The Clinical Research Ethical Review Board (CRERB) oversees research undertaken under the Veterinary Surgeons Act (VSA), other research projects on animals that do not fall under A(SP)A and clinical research studies on human subjects, to ensure the projects are ethically sound, scientifically robust and legal. This includes prospective clinical trials involving animals, other prospective animal research that does not fall within A(SP)A remit (e.g. Structure and Motion), behavioural studies or observational studies involving animals or humans, and work on biological samples collected from animals or humans, including work conducted with stored samples (e.g. stored urine, DNA, blood, pathological samples etc.) from past cases or other animals.
As part of the College's commitment to the Concordat on Openness, we are now publishing summaries of these types of study. These summaries aim to show the scope of the work being carried out at the College. This is an ongoing project.
Canine Chronic Enteropathy Archive
2024 2256-2: Canine Chronic Enteropathy Archive
Chronic enteropathy is the most common cause of long-standing gastrointestinal signs in dogs. Dogs with this condition can have a guarded prognosis, with some not responding to treatment. Currently, the underlying cause for this condition is unknown. Therefore, further studies are needed to help elucidate this, so that treatment that is more effective in this disease can be discovered. We propose creating an archive of residual plasma and faecal samples from dogs presenting with signs consistent with chronic enteropathy at the Queen Mother Hospital for Animals to then allow for future studies using novel methodology on these samples to help elucidate the underlying pathogenesis, which will then allow for advancement in the treatment of this disease.
Project approved: 26 February 2024
Duration: 5 years
The role of the anti-inflammatory mediator, adiponectin in protecting against SIRS-induced organ damage with particular reference to sepsis-related laminitis
Does early life experience affect injury risk and performance in later life?
2024 2251-2: Does early life experience affect injury risk and performance in later life?
The UK Thoroughbred industry is committed to ensuring the health and welfare of Thoroughbreds bred for the purpose of racing throughout their lifetime, including during early life and after they leave the racing industry. Available figures suggest that, over the past two decades, there has been little change in the proportions of horses entering training, appearing on a racetrack or winning prizemoney. Although it is thought that musculoskeletal disease and injury may be an important factor, there is as yet in the UK, very little evidence to explain either why some horses fail to achieve these milestones or where they go when they leave the industry. It has been established from human medicine that experiences in the womb and during childhood can have lasting effects and alter a person’s susceptibility to disease and injury in later life. In horses, experimental studies showed that both prolonged box rest and excessive high speed activity in foals can have detrimental effects on the development of bones, joints and tendons. As yet it is unknown whether any such early-life experiences might influence future athletic ability, racing performance and earning potential.
This work will use information from a group of young Thoroughbreds, who have been followed since birth, to (i) describe the proportions of horses that enter training and race, including reasons and destinations of any that do not and (ii) evaluate the effects of early-life health and exercise on horses’ career milestones and racing performance Foals were born in 2019 and 2020 and each day until they left the farm, details were recorded of any turn-out or exercise they received, episodes of illness or injury and routine procedures such as farriery. Each dam’s breeding and veterinary history were recorded from stud and veterinary records. Follow-up information about when horses entered training and raced will be collected from stud farms' records in cases where horses are still under the ownership of the original study participant. Additional sales, training, export and race performance records will be collected from studbook and racing authorities’ databases via non-disclosure agreements and other publically available sources (such as www.racingpost.com). Statistical modelling methods will then be used to evaluate relationships between early-life experiences, in particular exercise (turn-out), and whether or not horses enter training and their subsequent race performance.
Results can be used to optimise farm management and turn-out practices to produce more healthy and successful equine athletes, which can improve Thoroughbred health and welfare and help to ensure the future sustainability of the Thoroughbred breeding industry.
Date approved: 06 February 2024
Therapeutic plasma exchange in dogs with cutaneous and renal glomerular vasculopathy
2024 2246-2: Therapeutic plasma exchange in dogs with cutaneous and renal glomerular vasculopathy
Dogs diagnosed with cutaneous and renal glomerular vasculopathy (also sometimes called Alabama rot) who are treated at the Royal Veterinary College's Queen Mother Hospital for animals will have their anonymised case data used in a study to assess if therapeutic plasma exchange may be associated with any changes in survival. Therapeutic plasma exchange is a procedure used to manage similar diseases in people, although no evidence exists to prove a benefit of its use in dogs with cutaneous and renal glomerular vasculopathy.
The study aims to assess if animals who are managed at a specialist hospital have any difference in survival when treated with this procedure compared to without it. Although survival is extremely important, understanding if the procedure might have benefits in managing the disease regardless of survival (for example, some animals could have improvement in kidney function but be euthanised due to the severity of their wounds) and so assessing if several markers monitored routinely in dogs with the disease have a different change over time in dogs with the therapy compared to those who do not. Finally, for dogs who undergo the procedure an analysis will be performed to assess if some values (such as the volume of urine being made) at the time the plasma exchange is performed are associated with the chances of survival or halting disease progression.
Project approved: 06 February 2024
Is the oral sugar test useful as a predictor of corticosteroid-associated laminitis in horses?
URN 2023 2238-2 - Project Title: Is the oral sugar test useful as a predictor of corticosteroid-associated laminitis in horses?
Laminitis is a common condition in horses and can be associated with endocrine diseases such as equine metabolic syndrome (EMS) and pituitary-pars intermedia dysfunction (PPID or Cushing’s). These diseases can result in insulin dysregulation (ID) which causes an elevated blood insulin. The insulin damages the supporting apparatus of the foot, resulting in a condition call endocrinopathic laminitis. Unfortunately, it is not always easy to identify which horses have ID based on their external appearance alone but a straightforward diagnostic test, the oral sugar test (OST), can be used to assess a horse’s insulin status and whether they have ID.
It has been shown in a recent study that horses with ID might be more prone to develop laminitis following treatment with corticosteroids, but we need more evidence to determine if this is indeed the case. To do this, we will test horses that require treatment with corticosteroids using the oral sugar test and then follow them for a period of time to see if they develop laminitis or not. By analysing these results, we will be able to determine if the OST can be used to predict the risk of corticosteroid- associated laminitis in horses that require treatment with corticosteroids. If the risk was high in a horse, it would give owners the choice to elect alternative treatments for their horse, thus reducing the likelihood of their horse developing laminitis.
Date approved: 02 February 2024
Project duration: 5 years
Evaluation of ADAMTS 13 activity in dogs with CRGV using an ELISA method
2024 2243-2: Evaluation of ADAMTS 13 activity in dogs with CRGV using an ELISA method
Cutaneous and renal glomerular vasculopathy (CRGV) is a deadly disease that affects dogs in the UK since 2011. No underlying reason or mechanism has been discovered yet thus no definitive specific treatment is currently available and known to be effective in curing the disease. Similarities in the progression and type of clinical signs of CRGV in dogs with a disease in people, called Thrombotic thrombocytopenia purpura (TTP), suggests that these diseases could share the same mechanism. In people with TTP a reduction in a molecule called ADAMTS-13 leads to multiple clots forming spontaneously in different organs and leading to dysfunction.
Our study aims at measuring this molecule in healthy dogs using a human test to validate the assay in dogs in order to make sure that it is measuring in dogs what is meant to measure. We will also compare ADAMTS-13 concentration in dogs with CRGV with other patients with different disease processes and with healthy dogs. Our hypothesis is that dogs with CRGV will have much lower ADAMTS-13 concentration compared to dogs with other diseases, similarly to what happens in people with TTP.
Dogs included in the study will not have any additional blood sampling; the blood we are intending to use will only be the residual left over from blood sampled for clinical purposes only.
Project approved: 02 February 2024
Duration: 2 years
Sit-to-stand and sit-to-walk biomechanics in ostriches
2023 2239-2: Sit-to-stand and sit-to-walk biomechanics in ostriches
Our goal is to understand how birds, specifically ostriches, navigate the sit-to-stand (from fully crouched to upright) and sit-to-walk (from fully crouched to locomoting) motions—two critical yet understudied behaviours that involve large limb joint excursions and muscle forces.
By focusing on the ostrich, a large, fast-moving bird with unique limb proportions, we aim to uncover how their elongated hindlimbs and relatively short muscles manage these two behaviours. Feathers around limb joints will be trimmed, and harmless markers will be placed on the birds to track joint movements using motion analysis cameras. The birds will stand on force platforms, allowing us to non-invasively measure to the mechanics of these motions.
This research, while harmless and akin to mild exercise for the birds, holds strong potential beyond basic science. Insights gained could aid in understanding musculoskeletal issues in birds and contribute to broader knowledge in muscle physiology. Moreover, findings may offer insights into human limb disorders associated with range of joint motion or aging.
Project Approved: 02 February 2024
Duration: 15 months
The impacts of Progressive Retinal Atrophy-associated vision-loss on dog and owner Quality of Life
2023 2235-3: The impacts of Progressive Retinal Atrophy-associated vision-loss on dog and owner Quality of Life
Progressive retinal atrophy (PRA) is a leading cause of genetically inherited blindness in dogs. However, very little research has been done on the impacts PRA may have on the quality of life of the dog. Recent research suggests that vision loss is associated with negative impacts on a dog’s daily activities and emotions. Additional research suggests that eye contact is an important part of communication and bond between dog and owner. Therefore, vision loss may have a significant impact on the dog-owner relationship, on top of the psychological impact associated with the caregiver burden of looking after a chronically ill dog.
We aim to further examine the potential impact PRA has on the long-term emotional state of dogs, using behavioural tests that do not rely on owner judgements. The emotional impact of PRA on the dog will be determined via an optimism/pessimism judgement bias test. Humans and Animals experiencing long term negative states such as anxiety or depression show greater pessimism. Both dogs affected by PRA and healthy case-matched dogs not affected by PRA (and not already diagnosed with anxiety or depression) will be trained to expect a positive reward when one cue (e.g. a low frequency tone) is presented, and no reward when another cue is presented (e.g. high frequency tone). When subsequently presented with an ambiguous cue (e.g. mid-frequency tone), like humans, dogs experiencing chronic negative emotional states, such as anxiety or depression, will be more likely to respond pessimistically, i.e. as if they expect no reward. In addition, chronic stress will be assessed via a hair cortisol analysis. The degree of impact of PRA on dog vision will be determined by how quickly they can navigate a maze test in two different light intensities (as ‘night blindness’ occurs before ‘day blindness’), as well as an eye examination by a trained veterinarian specialist.
If, as predicted, this study determines that dogs with PRA are more likely to show pessimism than healthy unaffected dogs and greater chronic stress the findings will support advice to vets and owners about treatment of these co-occurring conditions alongside vision loss and help to improve the daily lives of vision impaired dogs.
Project approved: 29 January 2024
Duration: one year
Evaluation of haemostasis in canine steroid responsive meningitis-arteritis using Viscoelastic Coagulation Monitor Vet (VCM-V)
2024 2244-3: Evaluation of haemostasis in canine steroid responsive meningitis-arteritis using Viscoelastic Coagulation Monitor Vet (VCM-V)
Steroid responsive meningitis-arteritis (SRMA) is a disorder commonly recognised in adolescent dogs. It is characterised by inflammation affecting the blood vessels and tissue surrounding the brain and spinal cord. Affected dogs can manifest with a stiff painful neck and marked fever. It is, however, a disease that can impact the whole body and abnormalities involving the heart, as well as inflammation affecting a gland in the neck known as the thyroid gland are reported.
The outlook for dogs with SRMA is relatively good with early and aggressive steroid treatment. Recently published case reports however have suggested that patients with SRMA might be at risk for spontaneous bleeding inside and outside the nervous system. The reason is unknown. Coagulation status/ haemostasis (likelihood of bleeding) in these patients has not been explored. Evaluating coagulation status could help understand the disease better and prevent the spontaneous bleeding observed in some of these patients.
Project approved: 24 January 2024
Duration: 3 years
Canine leptospirosis: Improving molecular diagnostics and understanding of the epidemiology of disease in dogs
2023 2234-3: Canine leptospirosis: Improving molecular diagnostics and understanding of the epidemiology of disease in dogs
Leptospirosis is an infectious disease that affects both humans and animals. The infection can be passed between different animal species and also passed on to people. In dogs, there is a vaccine available, but this does not necessarily protect against all the different strains that are present in the environment and these might differ depending on the geographical location. For example, the strains present in North America are different to the ones in the UK and we have collaborators in Nigeria and South Africa, where there is virtually no information about the strains that are causing infection in dogs (and potentially passing on this infection to the human population). One way to diagnose canine leptospirosis is to analyse the DNA taken from clinical samples such as blood and urine, using the polymerase chain reaction (PCR). In human patients any PCR positive samples are further analysed to identify the specific strain responsible for the infection, but in veterinary medicine, this second stage is not currently available. At the RVC, we have set up the second stage diagnostic test and the aim of this research is to offer this service to diagnostic laboratories to help them with making a diagnosis of canine leptospirosis and also to use this information to evaluate which strains are causing the infection in the dog population, which will inform whether the canine leptospirosis vaccine needs to be updated to provide better protective immunity.
Project approved: 17 January 2024
Duration: 5 years
Is feline diffuse iris melanoma an accurate model of human uveal melanoma?
2023 2236-2: Is feline diffuse iris melanoma an accurate model of human uveal melanoma?
Uveal melanoma (UM) is the most common ocular tumour in adults and is devastating. Nearly half of patients die within 15 years of diagnosis, usually secondary to metastatic disease. Poorer outcome is associated with increased tumour thickness or local invasion. Feline diffuse iris melanoma (FDIM) is the most common ocular tumour of cats. Like human UM, metastasis of FDIM is more likely with larger, more locally invasive tumours. Genes responsible for tumour progression in UM and FDIM are comparable, suggesting that FDIM may be a good model for UM.
Feline tissue samples will be obtained from a pathology laboratory and RNA sequencing (genetic analysis) will be performed on early and late FDIM samples and compared to benign iris changes (‘iris melanosis’). This will allow us to understand the genetic changes that drive the formation of the tumour and those that lead to aggressive metastatic behviour. By understanding these genetic changes, we may be able to identify targets for new treatment options for cats and people with ocular melanoma.
Expected results (hypothesis/prediction)
• Using RNA-sequencing, the genetic landscape of (FDIM) can be defined
• Gene (RNA) expression differences can be identified between benign ‘melanosis’, early and late FDIM
• Molecular pathways and genetic transformations can be identified that drive tumour progression
• FDIM shows a comparable genetic mechanism as UM in humans
Project approved: 22 December 2023
Duration: 3 years
Imaging biomarkers of osteoarthritic cartilage disease
2023 2233-2: Imaging biomarkers of osteoarthritic cartilage disease
Dog osteoarthritis (OA) is a common cause of disability and pain. Early detection could ideally allow us to halt or slow OA and associated cartilage deterioration, yet current X-rays or scans only allow diagnosis of very advanced disease. We have pioneered use of super-high resolution CT scans (microCT) to examine the microscopic structure of bone below the arthritic joint surface in normal and OA dog hips. This has pinpointed the modifications in bone structure which have taken place in OA, enabling us to accurately predict exactly how much cartilage deterioration there is at the joint surface. Our scans also exposed small spherical structures, known as subchondral bone cysts (SBC), to be present only in OA samples. Surprisingly, SBC are not well described in dog OA. In human OA, powerful Magnetic Resonance Imaging (MRI) scanner use reveals ‘bone bruises’ (or bone marrow lesions, BMLs); areas of bleeding in the bone immediately below the joint only visible with MRI. BML are important as they cause pain, and it is likely from human studies that they develop into SCB. Our pilot work showing SBC in the dog, therefore leads us to speculate that BMLs would also have been present at an earlier stage. This research aims to determine whether BMLs are present in the dog femoral head, and to determine any relationship they have with the SBC we have already identified. Confirming BMLs would allow for earlier diagnosis of dog OA and a better understanding of their pain, ultimately increasing our treatment options.
Project approved: 07 December 2023
Duration: 5 years.
A transfer learning approach to intestinal image analysis differentiates treatment response in canine protein-losing enteropathy
2023 2237-2: A transfer learning approach to intestinal image analysis differentiates treatment response in canine protein-losing enteropathy
Protein-losing enteropathy in dogs is a gastrointestinal disease that has a guarded prognosis and can be treated using diet alone or diet with immunosuppressant medication. The prognosis for those cases treated with diet alone is more favourable. However, the ability to diagnose food-responsive cases from immunosuppressant-responsive cases at diagnosis is not possible at this time. Our study intends to use machine transfer learning on duodenal biopsy specimens that have already been collected and archived from diagnostic investigations of dogs previously seen at the Queen Mother Hospital for Animals to determine if this can retrospectively help to differentiate cases of food-responsive from immunosuppressant-responsive cases. Such information will help us to predict at the time of diagnosis those cases that will respond to food alone, which will allow a favourable prognosis and avoid the use of unnecessary medication.
Project approved: 30 November 2023
Duration: 1 year
Insights into the pathogenesis of equine metabolic syndrome: plasma amino acid and acylcarnitine profiles in ponies with insulin dysregulation
2023 2232-2: Insights into the pathogenesis of equine metabolic syndrome: plasma amino acid and acylcarnitine profiles in ponies with insulin dysregulation
BACKGROUND: Laminitis is a common and painful condition of horses and ponies. Most laminitis cases are caused by high levels of insulin in the blood. Blood insulin levels become excessively high if horses develop insulin dysregulation (a condition with similarities to type 2 diabetes in people). The underlying cause of insulin dysregulation is not understood but studies in people, and small studies in horses and rodents suggest it may relate to changes in the levels of acylcarnitines and amino acids in the blood. Acylcarnitines and amino acids are normal constituents of the blood but at high levels they may reduce the effect of insulin on muscle, fat and the liver. Higher levels of insulin are therefore required and insulin levels in the blood therefore increase.
METHODS: We will use surplus blood from a previous study (carried out at the RVC) into laminitis in which blood samples were collected from ponies with and without insulin dysregulation at 6 monthly intervals over 4 years. We first plan to adapt a kit routinely used to measure acylcarnitines and amino acids in human babies for use with equine blood samples. We will then use this kit to compare the levels of acylcarnitines and amino acids in samples from the previous study that come from 50 ponies with and 50 ponies without insulin dysregulation. In the 50 ponies with insulin dysregulation we will also compare samples from the time at which insulin dysreglation was apparent with samples taken a year earlier to reveal more about how insulin dysregulation develops.
BENEFITS OF THE STUDY: Our overarching aim is to identify horses at risk of laminitis at an earlier stage and to understand the process by which insulin dysregulation develops such that we prevent it.
Project approved: 29 November 2023
Duration: One year.
Longitudinal health screening of mature, senior and geriatric cats
2023 2225-3: Longitudinal health screening of mature, senior and geriatric cats
Chronic kidney disease (CKD), hyperthyroidism (overactive thyroid gland), high blood pressure (hypertension) and urinary tract infections (UTI) are common conditions affecting ageing cats and are frequently diagnosed and managed by veterinary surgeons in primary care practice. These conditions can occur independently or concurrently and all have substantial impact on quality of life.
Longitudinal health screening of mature, senior and geriatric cats has been offered at the Beaumont Sainsbury’s Animal Hospital (Camden) and the People’s Dispensary for Sick Animals (Bow), under ethical approval obtained from the Royal Veterinary College since 1998. This health screening has permitted identification of cats with the conditions outlined above and evaluation of clinical information from these cats has enabled us to gain a better understanding of the epidemiology of these disease conditions and to contribute to the current international recommendations for the earlier diagnosis, long-term care and treatment of cats with CKD, hyperthyroidism, hypertension and UTI.
The clinics offer health screening to mature (7-10 years), senior (10-14 years) and geriatric (≥15 years) cats similar to screening that would be provided through many primary care veterinary practices and as advocated by Cat Care for Life associated with the International Society of Feline Medicine and International Cat Care. As part of our health screening clinics, we are able to speak with clients to obtain a full history about their cat including evaluation of a lifestyle questionnaire. All cats will receive a full physical examination including measurement of blood pressure with evaluation of the eyes if there is concern for hypertension. For all cats we offer to perform a blood and urine sample check allowing us to evaluation for the early diagnosis of CKD, hyperthyroidism and UTI.
For those cats that are deemed healthy at the time of assessment, routine 6 monthly re-examination appointments are offered. Those cats diagnosed with CKD, hyperthyroidism hypertension and/or UTI are offered continued monitoring and treatment using standardised protocols that reflect best current evidence for the remaining life-span of the cat or for the duration of the period that the client wishes to remain part of the feline clinic. Once stabilised on appropriate therapy, patients diagnosed with CKD, hyperthyroidism and/or systemic hypertension are offered re-examination appointments every 8 weeks with routine biochemical and urinalysis monitoring performed at every other visit (q 16 weeks).
The clinic appointments, blood pressure assessment and laboratory diagnostic tests are all offered free of charge to the clients and are supported by external funding. For those cats diagnosed with CKD we are able to offer a stage specific commercial kidney diet (wet and dry versions) free of charge. Residual sample (plasma/serum/DNA cell pellet/urine/urine sediment) is stored from visits where sampling is performed. At the time of euthanasia, we are able to offer clients the option to donate their cat’s body for post-mortem examination and with informed consent during this procedure collect and store tissues that may assist with future studies of disease conditions affecting the ageing cat.
This feline clinic offers a very important and world recognised resource for the study of the ageing cat and, in particular, the common and clinically relevant disease conditions CKD, hyperthyroidism and systemic hypertension. The longitudinal monitoring of these older cats and the storage of residual samples, DNA cell pellets and post-mortem tissue offers the opportunity to improve our knowledge of the mechanisms that contribute to disease development and progression and to improve our ability to both diagnose and treat these conditions. Through our work we are able to provide clients and their cats with an early diagnosis of these key conditions, to gain a better understanding of environmental and clinical risk factors for these conditions, to optimise treatment and management of the cats that we are caring for all with the ultimate goal of improving the quality of life and welfare of older cats.
Continuation of existing project for another 5 years: approved 29 November 2023
A solution right under our nose? Exploring health implications and public demand for brachycephalic ‘designer’ outcrosses
URN 2023 2220-2: A solution right under our nose? Exploring health implications and public demand for brachycephalic ‘designer’ outcrosses
Extreme brachycephalic (flat-faced) dog breeds are continuing to increase in popularity with dog owners, despite their well-advertised health concerns. Leveraging the current popularity of ‘designer crossbreeds’ (intentional crosses between purebred-breeds) offers one route to shifting demand towards more-moderately shaped dogs. However, the health-status and public attitudes towards brachycephalic-outcrosses are poorly understood. The aim of this project, therefore, is to investigate the conformation, health status and public perceptions of ‘designer’ brachycephalic-outcrosses compared to their extreme-brachycephalic parent breed in the UK. The researcher will gather physical data from dogs who have one brachycephalic parent. This will include measures of health characteristics such as breathing difficulties, skin disease and tail length. It will also feature questionnaires to the owners about factors such as their dogs' sleep, breathing and eating habits. This data will then be compared to existing data from purebred brachycephalic dogs, such as Pugs.
Date approved: 13 November 2023
Duration of project:18 months
Prospective, randomized, masked, multicentre clinical study using ultraviolet C (UV C) light as an adjunct treatment of infectious keratitis in canine and feline patients to determine tolerance and safety
URN 2023 2217-3: Prospective, randomized, masked, multicentre clinical study using ultraviolet C (UV C) light as an adjunct treatment of infectious keratitis in canine and feline patients to determine tolerance and safety
Infectious corneal ulcers can represent a serious, vision-threatening condition, which is rapidly progressive and can even lead to perforation of the cornea and in the worst cases loss of the eye. Bacteria produce enzymes that digest (melt) the cornea. The conventional care protocol involves aggressive treatment with topical antimicrobial agents and anti-collagenases to stop the enzymes melting the cornea. However, there is a risk that antimicrobial use can select for antimicrobial resistance making the conventional treatment ineffective.
In light of the worldwide increase of antibiotic resistance and the discovery void of antibiotics in the last 30 years we aim to investigate if ultraviolet C (UVC) light may be a game changer in the treatment of infected corneal ulcers via its ability to act as a disinfectant. UVC light induces damage in DNA of microorganisms. Microorganisms, unlike healthy cells, don’t have repair mechanisms capable of repairing DNA damage and subsequently die. The antimicrobial effect of very low doses of ultraviolet C light has been shown both in vitro against a wide range of bacteria (including multidrug resistant isolates), viruses and fungi and in vivo in mice. Safety studies have shown no deleterious effect on healthy corneal cells and the low tissue penetration rate of UVC prevents damage of intraocular structures. The effect on the eye as far as DNA damage is concerned the same as 1 minute sunlight exposure. The UVC light treatment can be performed conscious and unlike in other ultraviolet light treatment no sedation is required due to the very short treatment time of a few seconds.
This study has the objective to determine if UVC light used in vivo will be tolerated and safe to use in patients with infectious keratitis. The patient will receive the gold-standard medical treatment. This consists of topical antibiotic eye drops chosen based on cytology, culture and sensitivity results, eyedrops that inhibit the enzymes responsible for melting and in addition pain relief. The frequency of medication will be adjusted to the individual requirements of the patient and based on the results of the re-examination. If the pet is assigned to the UVC light group, it will receive the UVC light treatment in addition. The assignment is random, and the examiner will be masked. Rescue UVC light treatment will be suggested if the initial medical treatment is not successful. To assess if the UVC treatment is safe, we are going to investigate its impact on the healing process, monitor for side effects of and compare the treatment outcome between the two groups. The information on this will be collected by performing a complete ophthalmic examination five times. This is the same approach as we would take for routine monitoring of the corneal healing process.
Long-term, this research project will help us find a new treatment option for patients with infectious keratitis, reduce antimicrobial use and potentially also prevent loss of eyes that have infections with the most resistant bacteria. Patients could benefit from a reduced frequency of topical medication, a shorter duration of hospitalisation and not requiring advanced corneal surgery under general anaesthesia with extensive scar tissue formation
Date approved: 05 October 2023
Duration of project: Two years
Inter-rate agreement between three thoracic ultrasonography techniques in preweaned dairy calves
2023 2215-2: Inter-rate agreement between three thoracic ultrasonography techniques in preweaned dairy calves
The aim of this project is to assess the inter-rater agreement between operators using different Thoracic ultrasonography (TUS) scoring techniques on healthy and unhealthy preweaned dairy calves and to measure the examination duration for different TUS methods.
One recently validated method for the early detection of bovine respiratory disease is thoracic ultrasound (Buczinski et al., 2013). This method allows for the identification of individual animals prior to the onset of clinical signs, which may be useful to allow early treatment and diagnostic sampling. The technique is also useful for assessing the success of therapy, and for monitoring or investigating disease prevalence at the herd level (Pardon, 2023). The originally described technique involves scanning the entire thorax of each calf on both sides, which, although thorough, can be time consuming. In light of this, other faster techniques have been proposed, which seek to reduce the time required per examination whilst minimizing any losses in accuracy. Whilst these techniques are likely to be especially useful for veterinary clinicians, there is minimal research available to them comparing their relative effectiveness, when performed in a real-life scenario.
Approved: 21 August 2023
Duration: 3 years
Integrating metaviromics with epidemiological dynamics: understanding rodent virus transmission in the Anthropocene
2023 2205-3: Integrating metaviromics with epidemiological dynamics: understanding rodent virus transmission in the Anthropocene
Most emerging infectious diseases affecting humans, including AIDS, influenza, and COVID-19, are caused by RNA viruses originating from non-human animals. In recent years, such 'zoonotic' viral diseases have become more common and widespread, a pattern frequently attributed to increasing environmental change. Notably, escalating human activity has destroyed and disrupted wild animal habitats by converting natural landscapes into agricultural farmlands and urban environments. As a result, we have drastically altered wild animal communities and how viruses circulate within these communities while simultaneously increasing our exposure to new animal viruses by eliminating historical ecological barriers separating species. Temporal changes in the environment, such as seasonal variation or climate change, can also alter pathogen prevalence in wild animal populations and influence zoonotic risk.
Despite significant research on viral zoonoses, actionable, real-world predictions of virus spillover risk remain elusive. A critical barrier to preventing and controlling future viral zoonoses is a lack of basic knowledge about how physical and temporal differences in the environment impact virus transmission within wild animal populations and how changes in viral transmission and community composition translate to human risk.
Attaining a predictive understanding of the dynamics of zoonoses within their animal reservoirs is a precondition to anticipate emergence or devise interventions that prevent emergence. However, financial and logistical challenges in studying high-risk viruses in wild animals - from the need for regular monitoring of individuals to the costly biosafety precautions involved - currently impede such understanding in most wildlife disease systems.
We will address these challenges by focusing on wild rodents, which are important viral reservoirs globally, responsible for more zoonoses than any other mammalian order, and represent well-studied and tractable systems for understanding the environmental impact on zoonotic virus transmission. Many rodents live in close proximity to human populations and are highly responsive to environmental change, both in their population dynamics and via behavioural changes that increase contact with humans. However, despite this circumstantial evidence, the underlying ecological mechanisms driving virus transmission within wild rodent populations remain hypothetical and, importantly, are far from predictive. This project will investigate how viruses circulate in wild rodents using established field studies in England and Uganda, which monitor wild rodent communities over time and space:
1) To tackle the practical challenges of studying viral transmission, we will develop new tools to infer epidemiological dynamics and zoonotic risk from increasingly accessible and low-cost host virome data. This flexible approach will allow rapid discovery and monitoring of zoonotic viruses by enabling epidemiological inferences from cross-sectional samples and guidance for appropriate sampling strategies to interpret metaviromic data in new host systems.
2) Using a long-term capture-mark-recapture wild study in Oxfordshire, UK, we will determine how seasonal environmental change influences rodent viral communities.
3) We will use field sites along a gradient of land cover in Uganda to understand how physical environmental change influences the risk of zoonotics in rodent communities. Specifically, we will identify local and landscape drivers of zoonotic hazards and how humans change behaviour to affect zoonotic risk across this gradient.
Together, this research will substantially improve our understanding of viral pathogens within key reservoir hosts and identify important environmental drivers that increase zoonotic risk.
Date approved: 04 August 2023
Study duration: 4.5 years
Improving the welfare of translocated individuals: European mink as a case study
2023 2210-2: Improving the welfare of translocated individuals: European mink as a case study
Captive-born individuals in conservation breeding programmes that aim to reintroduce them into the wild can show signs of behavioural impairments consistent with negative welfare states induced by the captive environment, jeopardising conservation efforts and raising societal concern. Further, welfare is typically not assessed after release, making it difficult to evidence how pre-release welfare impacts not only survival post-release but also the welfare of the individuals once established in the wild. We will study how two behaviours - play and abnormal repetitive behaviours, such as pacing - that respectively indicate positive and negative welfare states affect post-release welfare in the critically endangered European mink. In addition, we will aim to benchmark their welfare against that of existing wild populations of the species.
Methods for captive data collection have received RVC ethical approval from a sister project: c. 40 mink (20 in two specialist facilities) are being raised in welfare-improving conditions and data on relevant behaviours and physiological measures non-invasively recorded. Here, we seek approval for data collection immediately pre-release and following release of these individuals, and data from wild populations of the species, as follows:
As part of the on-going release programmes, independent of our study, released animals are fitted with radio-collars, radio tracked, and trapped twice per year. We will obtain activity data from the radio-collars and record data on individual levels of exploratory behaviour pre-release and immediately post-release by remote video-recording of the individuals' reaction to a novel object.
For the wild population, camera traps will be set in known dens and at release sites, at times where comparisons between captive and wild data are most relevant (i.e. naturally occurring stress-inducing events such as weaning and dispersal). Activity areas along water-courses (European mink are semi-aquatic) will be located and camera traps placed by occupied dens, with a natural object (e.g. wood stump) placed at a fixed distant from the den. From camera trap videos and images, we will collect relevant behaviours (e.g. frequency of play behaviour between dam and litter, and between litter mates, time spent investigating the focal object).
For both the released individuals and the existing populations of wild individuals we will also collect data on survival in the wild and cause of death.
This study will be the first of its kind, with implications for individuals involved in the increasing numbers of conservation breeding programmes (including 're-wilding' programmes) in the UK and overseas.
Date approved: 27 July 2023
Study duration: 3 years
Characterising the genetic architecture of equine exertional rhabdomyolysis
2023 2203-2: Characterising the genetic architecture of equine exertional rhabdomyolysis
Exertional rhabdomyolysis (ER) is a syndrome involving painful, exercise induced episodes of muscle stiffness which in the most extreme cases can lead to death. ER is seen in humans, most commonly athletes or military personnel, as well as dogs, however horses seem to be most affected by this syndrome. It is mostly commonly seen in racehorses, with other popular leisure horse breeds also affected. We believe there is a variety of genetic causes predisposing to the disease.
Muscle types can be split into those that are used for moving (active) and those that provide stability. The "active" muscles are mainly affected by the disease. We hypothese that something unique exists in these 'active' muscles that cause ER . In order to test our hypothesis we are comparing 'active' with 'stabilising' muscles from Warmblood and Thoroughbred horses as well as muscle from healthy and ER horses. By understanding how or why this syndrome occurs we would become better able to manage the condition and thereby improve the health and welfare of the affected animals, as well as allowing them to continue performing to the fullest of their capabilities.
Date approved: 27 July 2023
Study duration: 5 years
Empirical assessment of welfare in wild American mink and Eurasian otters: the effects of intra- and inter-specific population density
2023 2211-2: Empirical assessment of welfare in wild American mink and Eurasian otters: the effects of intra- and inter-specific population density
The aim of this project is to assess whether different population densities of conspecifics and competitors affect the welfare of mink and otters in the UK.
We will carry out field data collection for two years, during which we estimate to be able to sample c. 240 individuals (c. 10 individuals per species per site per year).
Our study will show whether the welfare of mink is negatively impacted in the presence of high densities of otters, and whether both species’ welfare is compromised at relatively higher densities of conspecifics. It will also provide a better understanding and identification of optimal non-invasive welfare measures for future studies of welfare in wild animals.
Date approved: 27 July 2023
Duration: 2 years
Investigating the efficacy of pregabalin, compared to gabapentin, at producing anxiolytic effects and facilitating intravenous blood sampling in cats
2022 2160-3: Investigating the efficacy of pregabalin, compared to gabapentin, at producing anxiolytic effects and facilitating intravenous blood sampling in cats
This study will aim to evaluate the effectiveness of a new medication, pregabalin, at reducing stress and anxiety (anxiolytic) experienced by cats during a procedure. Current clinical standard is to administer a drug called gabapentin, which has been shown to be effective at producing mild sedation and reducing anxiety in cats. This assists with reducing stress associated with transportation to the veterinary clinic and also undertaking common clinical procedures such as examination, blood sampling and placement of intravenous catheters. Pregabalin has a similar molecular structure and therefore similar effects to Gabapentin. However, a new formulation became available in a liquid formulation in the EU. This enables more accurate dosing as well as easier administration to cats.
This study aims to investigate whether pregabalin is as effective as gabapentin as an anxiolytic facilitating blood sampling in cats. Cats that are undergoing chemotherapy on a weekly basis as the QMHA will be recruited. Only cats that have been evaluated at least twice already by the oncology service and which have been deemed to require gabapentin will be enrolled in the study. Cats will act as their own controls, they will be randomised to receive either pregabalin or gabapentin and at their subsequent visit will be crossed over into the other treatment group.
The primary outcome will be if blood sampling was successful on first attempt, secondary outcomes assessed will include ease of handling, sedation scores and ease of travel to the veterinary clinic. Further, residual blood from samples obtained as part of patient monitoring required for chemotherapy administration, will be used to confirm correct administration of the treatment; concentration of gabapentin and pregabalin will be quantified in order to confirm that the intervention has been received by the cat. Cats will be closely monitoring during and after treatment administration and any adverse reactions closely document and reported if necessary.
This study will benefit the welfare of cats because, if pregabalin is as effective as gabapentin, it will represent a veterinary licenced product that is potentially easier to modify dosage (liquid versus tablet) and easier to administer in cats requiring an anxiolytic medication for veterinary treatment.
Date approved: 18 July 2023
Study duration: 1 year
Studies on the natural history and progression of acquired mitral insufficiency in the dog
2023 2207-3: Studies on the natural history and progression of acquired mitral insufficiency in the dog
Mitral valve disease is the most common cardiac disease affecting pet dogs. Factors influencing the development and progression of the disease remain incompletely understood and further research is necessary to better characterise the condition. I
t is recommended by experts that dogs at risk of the condition, or already known to be affected by it, are monitored at regular intervals for evidence of development or progression of disease. Early intervention in the pre-clinical stage of the disease is known to be of benefit, so actively monitoring patients can be of direct value to the patient being monitored and potentially result in improved quality of life and longevity.
The "mitral valve clinic" at the RVC is a longitudinal clinical research study through which dogs known to be affected by the condition, or at risk of development of the condition are monitored at intervals of approximately six months. This clinic has been running since 2004 and has recruited over 600 dogs. Dogs participating in the study benefit from monitoring by a cardiology specialist free of charge. All tests performed on participating dogs are standard clinical procedures and for the direct benefit of the dog on which they are being performed. These include taking a history, performing a physical examination, measuring blood pressure, taking a blood sample, collecting a urine sample, recording an ECG and performance of a cardiac ultrasound examination. All of these are done with the patient fully conscious. If a dog shows evidence of distress during any of the procedures performed then the examination is stopped. By compiling information about a large number of dogs over a long period of time more can be learned about the development and progression of the disease. Studying markers in residual blood and urine samples taken from clinic patients can help researchers to develop tests that maybe of direct value in diagnosis or prediction of progression in the future. The clinic has already contributed significantly to understanding of mitral valve disease having resulted in a number of publications and presentations at international meetings.
Date approved: 11 July 2023
Study duration: 5 years
Identifying novel antibody targets and patient subgroups in acquired myasthenia gravis in dogs
URN 2023 2188-2: Identifying novel antibody targets and patient subgroups in acquired myasthenia gravis in dogs
Acquired myasthenia gravis is an immune mediated disease. Affected dogs typically develop an inappropriate immune response to the acetylcholine receptor at the junction between their muscles and nerves. This results in disrupted signalling between nerves and muscles and muscle weakness. A canine specific test is available through a Neuromuscular Laboratory in California, in which the pathological antibodies can be detected in blood samples. However, we have recently seen dogs that are negative for acetylcholine receptor antibodies. In humans, a more sensitive test to detect acetylcholine receptor antibodies has been developed and additional antibody targets have been detected, such as MUSK.
In this study we plan to evaluate dogs that are negative for acetylcholine receptor antibodies but whose clinical presentation is consistent with myasthenia gravis. We hypothesise that these "seronegative" dogs are 1) more common than previously reported, 2) a proportion has autoantibodies against the acetylcholine receptor that were previously missed with conventional testing or have antibodies against other proteins with roles in neuromuscular transmission and 3) that treatment should be tailored to optimise outcome in these cases.
Our study objectives are:
1) Search the clinical database in order to obtain a full clinical description of canine myasthenic patients, including seronegative patients. Contact veterinarian and/or owners to obtain long term information, such as response to therapy, percentage remission, survival time.
2) To collect residual serum (1 ml) and EDTA blood (0.2 ml) from dogs presented to the QMHA with suspected myasthenia gravis (as well as healthy dogs and dogs with other immune-mediated disease as negative controls) and store at -20C.
3) The cell based assays prior to testing the banked samples will be optimised.
The data from this study could provide novel insights into the different causes and types of acquired myasthenia gravis, specifically novel antibody targets. Furthermore, optimized testing for autoantibodies could facilitate early diagnosis as well as patient stratification to support optimal treatment intervention and prognostication.
Start date: July 2023 for 3 years.
Approved: 11 July 2023
Terrestrial locomotor biomechanics in Indian gharials
URN 2023 2201-3: Terrestrial locomotor biomechanics in Indian gharials
As mechanical demands scale differently from capacities of limb muscles in terrestrial locomotion, land vertebrates modulate patterns of leg movement and limb posture across body size. Specifically, larger mammals and birds walk with higher relative stride frequencies and shorter relative stride lengths at equivalent relative speeds and more upright limb posture to address increases in mechanical demands. However, such size-dependent changes in the terrestrial locomotion have rarely been tested in ‘sprawling’ animals (e.g., crocodylians and lizards).
Our previous study on the terrestrial locomotion of American alligators showed that they follow the scaling patterns of leg movement and limb posture observed in mammals and birds, suggesting that erect animals that move their limbs along the sagittal plane (mammals and birds) and sprawling animals that move their limbs non-parasagittaly (crocodylians) experience the same size-dependent biomechanical constraint. However, whether observed changes in locomotor biomechanics across body size in American alligators are shared in other sprawling taxa with different body shape remains unknown.
In this project, we aim to understand size-dependent changes in terrestrial locomotion of Indian gharials (Gavialis gangeticus) that have the widest hip and shortest limbs among living crocodylians. This will enable us to make comparisons with our previous data from American alligators and provide insights into how different body shape affects terrestrial locomotion in sprawling animals. We will use juvenile to subadult Indian gharials in Deori Gharial Headstart Center, India, to measure 3D limb joint angles, ground reaction forces, and mass properties.
We hypothesize that Indian gharials would follow the scaling patterns of leg movement and limb posture observed in mammals, birds, and alligators to address size-dependent increase in mechanical demands. However, we also expect shape-related differences in locomotor stability and capacities. In the longer term, the locomotion data from Indian gharials will be compared with the results of computer musculoskeletal simulation to illuminate size-dependent changes in muscle force and work capacities and limb bone strains, which will in turn help understand the evolution of locomotion in relation to body size and shape in birds, crocodylians, dinosaurs, and their kin.
Start date: July 2023 for 1 year
Approved: 06 July 2023
Optimization of culture condition for equine in vitro maturation of oocytes
2023 2206-2: Optimization of culture condition for equine in vitro maturation of oocytes
This project aims to develop techniques for assisted reproductive technologies (ART) for equines. These include in vitro maturation (IVM), in vitro embryo production by in vitro fertilization (IVF) or intracytoplasmic sperm injection (ISCI).
We will collecting oocytes (eggs) from ovaries of mares, which will be cultured in the lab in order to gain important insight into the function including normal maturation and fertilization activity. It will also help us understand how the oocyte become ready to be fertilized by a sperm and form an embryo.
Start date: 1 July 2023 for 5 years
Project approved: 27 June 2023
Limb stiffness in fore and hind limbs and after superficial digital flexor tendon and suspensory ligament injury – a clue to limb function and injury response?
URN 2023 2204-2: Limb stiffness in fore and hind limbs and after superficial digital flexor tendon and suspensory ligament injury – a clue to limb function and injury response?
The mechanical properties of a horse’s limb can be measured by attaching a goniometer (a device which measures angles) to a horse’s leg and standing the horse on portable floor scales. This method has been shown to be correlated to the stiffness of the horse’s limb, which is largely dictated by two soft tissue structures, the superficial digital flexor tendon and the suspensory ligament. These two structures are commonly injured in performing horses, and further understanding of the mechanical properties of these structures and their response to injury is required in order to improve monitoring of injuries and recovery, as well as further understanding the prevention of these injuries. Limb stiffness measurement is non-invasive and can be performed in an unsedated horse.
The aims of this project are to establish if limb stiffness is the same in front and hind limbs, and if it is correlated with age in uninjured horses. It also aims to collate data from horses with soft tissue injuries to establish if there are long term changes in limb stiffness following injury. This project involves the use of retrospective limb stiffness data, collected from horses with soft tissue injuries as part of their clinical monitoring. It also involves the use of limb stiffness data gathered from uninjured horses as part of a previous research project for which ethical approval was granted. Further data may need to be collected from the RVC teaching herd if the retrospective data on normal horses is found to be inadequate (too few samples, or too narrow age range). Consent for this will be obtained.
Project approved: 22 June 2023
Duration: 1 year
The role of different pasture types on ewe and lamb performance and worm burden
2023 2190-2: The role of different pasture types on ewe and lamb performance and worm burden
Sheep farming is an important part of the agricultural sector in the United Kingdom (UK) and a valuable contributor to the national economy. With increasing pressure on our food producing animal farms to be more sustainable and resilient in the face of future shocks and stressors such as climate change, subsidy changes and an increasing population to cater for, now is the time more than ever to identify areas of practice that increase efficiency, performance, health, welfare and therefore sustainability and resilience on farms. The national sheep flock was reported to be 33,066,000 in 2022, an increase of 0.3% from 2021, with almost half a million people working on commercial farms. Of this number lambs account for almost half, so therefore are an important and key part of the population. Therefore this project aims to explore the impact of different grazing pasture types; leucerne, herb lay and a more traditional grass/clover mix. At the time of weaning 50 lambs will be grazed on each pasture type and weight, interbal worm burden, lameness and other characteristics will be measured at the start, during and at the end of the grazing period.
This pilot study will help to provide data to start exploring the impact of different grazing pastures on lamb health and welfare and therefore farm efficiency, profitability and sustainability.
Approved: 23 May 2023
Duration: 8 months
Direct investigation of whether lop-eared conformations predispose rabbits to ear and dental disease: a pedigree population study
2023 2198-3: Direct investigation of whether lop-eared conformations predispose rabbits to ear and dental disease: a pedigree population study
Lop-eared rabbits may be predisposed to ear and dental disease, according to recent studies of rescue and clinical rabbit populations. However, the studies were small-scale or retrospective, the rabbits’ histories unknown and owner-reported breeds unverified. Brachycephaly may also predispose to dental problems so it is important to compare lops with erect-eared rabbits of similar facial length.
We aim to investigate lop-eared conformations as risk factors for ear and dental disease in British Rabbit Council (BRC) show populations of rabbits, thanks to funding from the Animal Welfare Foundation and Animal Care Trust. We will attend BRC shows and rabbit studs, with in-kind BRC support, and will systematically assess ear and dental health and facial length in rabbits of representative breeds. An otoscope will be used to visualise the ear and mouth of each rabbit. A BRC veterinarian will also independently assess a subset of rabbits to allow inter-observer agreement to be tested. The data will be used to analyse whether breed-related conformations are risk factors for either outcome, accounting for rabbit age, sex, and size. Findings will be used to assist rabbit breeders to develop targeted breeding strategies to improve rabbit welfare, where needed, and to highlight any good practice.
Approved: 16 May 2023
Duration: 1 year
Comparison of cardiovascular and sedative effects of Zenalpha to Medetomidine during routine diagnostic imaging procedures
2023 2189-3: Comparison of cardiovascular and sedative effects of Zenalpha to Medetomidine during routine diagnostic imaging procedures
Commonly used sedation protocol in dogs for short procedures such as X-rays contains Medetomidine (an alpha-2 agonist) combined with an opioid (such as butorphanol). An opioid is added as the combination allows for reducing both doses and reducing side-effects and provides synergistic effects. This protocol provides reliable sedation but also brings some cardiovascular side-effects such as reduced heart rate and increased blood pressure. The effects of sedation begins with a 10-20 minutes onset of action and may last longer than 60 minutes. A reversal agent exists to reverse the effects of sedation at the end of procedure to allow faster recovery however cardiovascular side-effects may linger.
A new product Zenalpha, contains Medetomidine and a peripheral reversal agent Vatinoxan that will reduce the unwanted cardiovascular side-effects of medetomidine. The addition of vatinoxan in the new product also allows for faster onset of action and shorter duration of sedation, and thus less need for reversal.
We aim to compare the new product zenalpha to the traditional product medetomidine both used in combination with an opioid (butorphanol). We will measure the cardiovascular and sedative effects to quantify the differences between the protocols.
Cardiovascular safety profile of Zenalpha is improved compared to traditional Medetomidine according to previous studies. However more research is required with normal clinical use of combination drugs to produce more clinically applicable data for day-to-day veterinary practice use.
Our hypothesis is that the administration of Zenalpha with an opioid compared to Medetomidine with an opioid will provide improved cardiovascular stability (heart rate and blood pressure) during routine non-painful procedures (X-rays, Ultrasound, CT). In addition, a reduction in onset and duration of action of sedation will be demonstrated and would improve patient safety, work efficiency and practice work flow.
Date approved: 15 May 2023
Duration: 2 years
AdapTB - Defining the Molecular Determinants of Mycobacterial Adaptation and host:pathogen Interaction to inform bTB control
2022 2128-3: AdapTB - Defining the Molecular Determinants of Mycobacterial Adaptation and host:pathogen Interaction to inform bTB control
Bovine tuberculosis (bTB) in cattle is both an economic and public health risk. A better understanding of how the pathogen that causes bovine TB interacts with the bovine host is needed to inform control measures. bTB is caused by a bacterium called Mycobacterium bovis (Mb). Upon infection, cattle can respond in several ways resulting in different pathological effects. Usually, bTB is confined to the lungs however, the spreading of Mycobacterium bovis to sites outside of the lungs is associated with poor disease control and higher transmission risk. Even if bacterial replication is initially contained (in pathological structures called granulomas) bacteria can sometimes persist at these sites. Failure to prevent bacterial replication at these sites can lead to lesion breakdown and spill-over of bacteria into the airways resulting in onward transmission. Additionally, bacteria can spreadto extra-pulmonary sites, a situation which is common in zoonotic (caused by cattle-human transfer of pathogen) infections with Mb
Aims: The aims for which we seek approval is to identify the bacterial genetic factors involved in the spreading of Mb to extra-pulmonary sites.
Benefits and long-term goals: The benefits of the research include a better understanding on the molecular mechanisms underlying disease dissemination in bTB. This work is complementary to genomic surveillance programs that are documenting the genetic changes in field strains of Mb. In the long term, this work will allow us to interpret the functional relevance of some of the single nucleotide polymorphisms in circulating strains of Mb.
Approved: 12 May 2023
Duration: 3 years
Comparative Endocrine Tumour Archive and Research
2023 2193-2: Comparative Endocrine Tumour Archive and Research
An improved understanding of endocrine conditions should aid us to improve the welfare of affected individuals and reduce the mortality of the disease in affected cats and dogs. Diseases caused by endocrine disorders can cause significant morbidity and mortality in cats and dogs. There are several endocrinologically active tissues in the body such as the thyroid glands, parathyroid glands, adrenal glands, pancreas and reproductive glands. Conditions affecting these tissues are increasingly recognised and diagnosed in cats and dogs, but there is currently a limited understanding about the cause of this broad category of disorders. These conditions are more easily diagnosed in the latter course of the disease when clinical signs and biochemical aberrations are more marked, but can be challenging to diagnose in the earlier stages of disease. Understanding pathogenesis, improved early diagnosis and improved prognosis prediction is desirable to aid us to ensure the welfare of animals committed to our care.
Our goal would be to determine if there are blood, urine, faecal or tissue biomarkers that can be used as non-invasive diagnostic, prognostication or monitoring tools for endocrine disorders. We aim to store residual clinical blood, urine samples and tissues from cats and dogs. We have already separately obtained ethical approval for a component of the project. The samples would be used for the investigation of the molecular and genetic causes of their disease. The tissue samples would be collected from surgical tissues extirpated for the clinical benefit of the individual and archived until analysed. Endocrine tissues from individuals that may or may not have an endocrine disorders but who die / are euthanised would also be collected (where permission has been provided). Samples may also be collected from reproductive organs which are removed during routine neutering. The tissues from routine neutering procedures are typically disposed and therefore we believe banking these tissues should not impact patient welfare. We would aim to utilise residual tissues from ovariectomies (ovary), ovariohysterectomy (ovary and uterus) and castration (testicles). Informed written consent would be obtained from owners of any animal that had endocrine tissue archived with the aim for analysis at a later date.
We believe an improved understanding of endocrine disorder development and progression would hopefully allow earlier disease diagnosis or disease prevention. Identification of molecular mechanisms of disease may allow better use of existing drugs to manage non-surgical endocrine diseases and our scientific understanding of disease development and progression.
Project approved: 12 May 2023
Duration: 5 years
Genomic Analysis of HCM in Cats
2023 2192-3 - Genomic Analysis of HCM in Cats
Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease in humans (1 in 500) and cats (1 in 7), being strikingly similar in the two species, sharing both clinical and histopathological findings. Cats diagnosed with severe HCM can develop heart failure, painful paralysis due to thromboembolic complications, or sudden death which is highly distressing for owners alongside being a major animal welfare issue. Despite this, the risk factors and genetic architecture are not fully understood. Furthermore, the diagnosis of HCM is challenging for veterinarians due to the clinical heterogeneity of HCM and need for specialist testing to identify subclinical disease. In both cats and humans, HCM is heritable and previous studies in the Maine coon and Ragdoll cat breeds have identified two causal mutations also known to affect humans. However, these variants have not been found in other affected cat breeds.
This project aims to enhance feline and human health, welfare and longevity by increasing our understanding of the genetic and environmental risk factors driving disease severity in cats, and ultimately applying the results to HCM in human medicine. An owner-report questionnaire will assess environmental, personality and lifestyle factors affecting HCM susceptibility in cats. Moreover, we will use cutting edge genetic and genomic technologies (genome-wide association studies and whole genome sequencing) to identify genetic markers and causative mutations for feline HCM. The outcome of these studies will be compared with human data to assess their utility as disease models.
The aims of the present study are:
- To use residual blood or buccal swabs obtained at clinical examinations from cats with a known cardiac phenotype to extract DNA and RNA in order to perform genetic, genomic and transcriptomic analyses to look for mutations associated with HCM in cats.
- To identify risk factors of HCM through a cat owner-based questionnaire “Identifying environmental and lifestyle risk factors associated with the development of hypertrophic cardiomyopathy in cats”.
Genomic and transcriptomic studies could lead to novel HCM therapeutics of interest for the pharmaceutical and healthcare technology industries. The ongoing project will have social and economic impacts on both veterinarian and human medicine through implementation of the cat model in the One Health concept through development of improved disease diagnostics and interventions.
Project approved: 03 May 2023
Duration: 5 years
Investigation of equine endothelial cell function
2023 2191-2: Investigation of equine endothelial cell function
Endothelial cells form the innermost layer of blood vessels throughout the body and are essential for many different processes. One of these is angiogenesis, the formation of new blood vessels, which is important during growth, but also in response to exercise. My studies so far have developed methods for the study of angiogenesis in endothelial cells from horses, and I have used these methods to investigate the pro-angiogenic responses induced by exercise in racehorses. The experimental methods used so far are far removed from the natural processes that occur in the body so I plan to develop two new methods which are closer to what occurs naturally. Both these methods are used in human research so I plan to adapt them for use with horse cells and tissues. The cells and tissues required for these studies will be obtained from horses euthanised at an abattoir, so no additional animals will be sacrificed for this work. My work so far has identified important differences in the function of equine endothelial cells in comparison to human endothelial cells. These differences will allow the use of these new equine models to investigate diseases involving abnormal human endothelial cell function.
Project Approved: 25 April 2023
Duration: 5 years
Evaluation of Biomarkers for Assessing Response to Treatment and Outcome in Dogs with Immune-Mediated Haemolytic Anaemia - control dogs
2023 2187-2 - Evaluation of Biomarkers for Assessing Response to Treatment and Outcome in Dogs with Immune-Mediated Haemolytic Anaemia - control dogs
We would like to obtain left over blood samples (up to 0.5ml blood] from up to 10 healthy, blood donor dogs to use for controls for our prospective clinical study 'Evaluation of Biomarkers for Assessing Response to Treatment and Outcome in Dogs with Immune-Mediated Haemolytic Anaemia' (URN 2018 1779-2).
Currently, all canine blood donors are offered complete blood cell count and infectious disease testing annually, a blood sample is also taken for haemoglobin analysis to ensure the donor is not anaemic prior to donation. We would like to obtain the left-over samples from those blood sampling events to use as healthy controls for the above project. Owners of canine blood donors will give consent to residual blood samples to be used for research, using the QMHA consent form.
Approved: 04 May 2023
Duration: 4 months
Vitamin and acylcarnitine concentrations in horses with and without atypical myopathy
2023 2185-2: Vitamin and acylcarnitine concentrations in horses with and without atypical myopathy
We are investigating Atypical Myopathy, a serious disease of horses caused by a toxin found in sycamore seeds and seedlings. The toxin prevents horses from using fat to provide energy, causing energy failure in some muscles and death in around 50% of cases. Fats and their derivatives (acylcarnitines) that cannot be used by the horse accumulate in the bloodstream. We hypothesise that vitamins (in particular vitamin B2) help protect the horse from the effects of the toxin (hypoglycin A). The RVC currently receives diagnostic samples for assessment of hypoglycin conentration from horses suspected of suffering from atypical myopathy. We plan to measure the concentrations of vitamins, acylcarnitines (and other metabolites) in residual serum from these samples submitted for hypoglycin testing in order to understand more about why some horses die and others survive with this condition.
In order to interpret any differences we find in the samples the laboratory receives, we need to understand more about how sample handling can affect the levels of vitamins, acylcarnitines and other markers in the blood. We also need to investigate the normal levels of many of these compounds in apparently healthy horses.
The proposed study will form 3 sections. Each section will use residual blood/ serum/plasma from routine veterinary practice, either received by the RVC for measurement of hypoglycin A or collected at an Equine Veterinary Clinic (an equine practice providing intra-mural rotations for RVC clinical students)
1) Assessment of sample handing - residual blood collected from hospital patients will be handled differently to determine the effects storage at room temperature, delayed separation of blood, heparin and the effect of light on plasma on the analytes of interest. Blood is routinely sampled from many in-patients each morning and surplus (residual) blood will be used. Horses will not be blood sampled for the purpose of this study.
2) Normal ranges - after assessment of sample handling surplus blood/serum/plasma from 30-60 healthy horses will be used to determine normal ranges for analytes of interest. Common reasons for sampling healthy horses would include assessment of disease status prior to breeding or moving premises or for assessment of medications at pre-purchase examination.
3) Assessment of samples submitted to the RVC for hypoglycin A testing. Assuming acceptable sample stability we will analyse the concentrations of the analytes of interest in stored and ongoing submissions of hypoglycin diagnostic samples. We will assess associations between the severity of disease and concentrations of vitamins, acylcarnitines and other markers.
Project approved: 06 April 2023
Duration: 5 years
Micro computed tomography (micro-CT) for the assessment of the mitral valve compartment in a canine mode
2023 2183-2 - Micro computed tomography (micro-CT) for the assessment of the mitral valve compartment in a canine mode
Mitral valve disease (MVD) is a heart problem caused by a faulty heart valve. It’s the most common type of heart disease in dogs, especially in small breeds. When MVD reaches an advanced stage, the best treatment is surgery called mitral valve repair. This surgery involves making the heart valve ring (annulus) smaller through a procedure called annuloplasty, and placing artificial cords between the heart muscle and the valve leaflet edges, under cardiopulmonary bypass. The restoration of the correct annulus size is crucial. The aim of the study is to find the best location in the annulus (with the toughest tissue) to place the purse-string suture used to reduce the size of the annulus ring. To locate the toughest tissue in the annulus, a new diagnostic tool called Micro-computed tomography (Micro-CT) will be used. Micro-CT is a new diagnostic modality that enables three-dimensional (3D) imaging of complex soft tissue structures such as muscles and connective tissue (tough tissue); making it ideal for studying the annulus. The study involves the removing and the processing of the mitral valve compartment from dogs euthanised and donated to the Educational Memorial Program at the RVC; followed by the assessment of the annulus through a Micro-CT analysis.
Project approved: 21 March 2023
Duration: 5 years