Our Research

Inherited retinal degenerative diseases are a major cause of blindness worldwide. In these conditions, photoreceptors, the cells responsible for transforming light into a signal that can be transmitted to and interpreted by the brain, are dysfunctional and/or slowly destroyed.

Veterinary ophthalmologists and vision scientists from the Division of ExpeRTs are dedicated to identifying the genetic causes of inherited blindness, delineating the mechanistic basis of genetic visual defects, and developing innovative and effective treatments to preserve or restore sight to the visually impaired.

Through the use of canine models, the group has contributed to a better understanding of the molecular mechanisms leading to disease, and is contributing to the development of novel therapies for both dogs and people.

Over a hundred different breeds of dogs are affected with inherited forms of retinal degeneration that lead to progressive vision loss.

Two general approaches are used to identify genes associated with inheritable visual defects:

• A “candidate gene approach” where genes are selected based on their expected contribution to given disease characteristics
• A “genome wide screening approach” utilizing informative pedigree resources to identify the disease-bearing chromosomal region, followed by cloning and identification of the causative mutation

There are currently close to 35 different genes known to carry mutations responsible for retinal degeneration in dogs. Genetic studies carried out by Division of ExpeRTs investigators have identified mutations in many of these genes, and developed genetic tests that are helping veterinarians and dog breeders establish a molecular diagnosis and prevent these blinding diseases.

Learn more about how you can contribute to our ongoing gene discovery. 

Vision scientists at the Division of ExpeRTs are actively investigating the cascade of cellular and molecular events that are triggered in the retina by genetic mutations and environmental factors, and that subsequently lead to disease and death of rods and cones, the two classes of photoreceptor cells that are critical for vision. 

Analysis of specific pathways of cell death or cell survival enables identification of potential molecular targets for development of new therapeutic strategies. For example, identification of decreased levels of an anti-death gene called X-linked inhibitor of apoptosis (XIAP) in the degenerating retinas of dogs, has prompted our group to investigate whether XIAP supplementation via gene therapy can halt the death of photoreceptors.

Using state of the art transcriptomic technology, Division of ExpeRTs investigators have also discovered that numerous molecular signaling pathways of inflammation are activated in early and late stages of retinal disease in dogs, prompting to investigate the role of anti-inflammatory therapeutics in these neurodegenerative conditions.  

While the value of rodent models in vision research is undisputed, the complementary use of canine models offers many unique advantages.

In particular, the anatomy of the canine and human eye is quite similar and the presence of a  recently discovered cone-rich central retinal region (the canine “fovea-like area”), a well developed retinal vasculature, and comparable size advances the transfer of therapies developed in canine models to human patients.

Investigators from the Division of ExperRTs have studied more than 20 naturally-occurring canine diseases, most of which share striking similarities with their human equivalent, thus providing naturally-occurring models of Leber congenital amaurosis, early and late onset retinitis pigmentosa, achromatopsia (day blindness), cone rod dystrophy, and bestrophinopathy.

For further details please contact us.

Investigators at the Division of ExpeRTs have in collaboration with other academic and/or industry scientists pioneered the development of novel treatments for canine retinal diseases and their translation into several human clinical trials.

By using these canine models, they are able to evaluate in a human-sized eye the ability to successfully deliver drugs to the retina, demonstrate structural and functional rescue of retinal cells, preservation or restoration of visual cortical activity, and visually-guided behavior.

Following successful outcome with these proof of concept studies the Division of ExpeRTs is able to support non-clinical IND-enabling studies.