Project 15: Targeting diabetic vascular complications using a novel rat model for diabetic retinopathy

Diseases of the posterior segment of the eye are increasing considerably, in part due to an ageing population. One such disease, diabetic retinopathy, is the most common cause of blindness in working-age adults. Typical treatment involves regular injections into the eye, which is associated with significant patient discomfort and potentially serious side effects, including bleeding, infection and retinal detachment.

As such, there is an unmet clinical need for the development of new and improved medicines for diabetic retinopathy. One of the major challenges in drug discovery for diabetic retinopathy is the paucity of standardized and predictable animal models that allow for the testing of novel drug targets. This project aims to address this challenge through the development of a novel rat model that mimic the ocular complications of diabetes, including vascular leak, neovascularization and diabetic macular oedema. Research and experimental work will include in vivo ocular imaging and electrophysiology, molecular biology, drug formulation, and nanomedicine. The project is highly transdisciplinary in nature, incorporating biological, biomedical, medicinal, industrial and clinical expertise, as well as being highly relevant to patients and industry.

This project will include three international secondments, to a total of 9 months over the project lifetime. The secondments are to the University of Birmingham (UK), Loyola University Chicago (USA) and an industrial secondment to Nanovector srl. (Italy)

The main objectives of the research can be summarised as follows:

• To develop a novel rat model to mimic the ocular complications of diabetes, including vascular leak, neovascularization and diabetic macular oedema.
• To determine the effect of a high fat (Western) diet on the severity of ocular complications of diabetes
• To determine the feasibility of targeting the liver X receptor (LXR) as therapeutic strategy to ameliorate the ocular complications of diabetes.