Deciphering the role of the ocular glymphatic system in diabetic retinopathy

Diabetic retinopathy (DR) is a sight-threatening complication of diabetes.

Current treatments are designed to prevent further damage to retinal blood vessels but do not address the earlier stages of DR.

Patients with DR also have a higher risk of developing Alzheimer’s disease (AD) where there could be shared pathophysiological processes between brain and retina.

During AD, accumulation of toxic amyloid beta occurs due to dysfunction of the brain’s waste clearance system (the glymphatic system).

Although much less well described, the retina also possesses a glymphatic system which is dependent on integrity of the neurovascular unit (NVU) and especially on the homeostatic role of the Müller glia.

All cells of the retinal NVU are known to become dysfunctional during DR although we have little knowledge about the role of the glymphatic system during diabetes.

Understanding this will provide an important therapeutic opportunity and also go some way to explaining the established linkage between visual and cognitive decline, especially in type 2 diabetes. The aim of this fellowship proposal is to investigate the retinal glymphatic system in the context of DR.

I will test the hypothesis that damage to the retinal glymphatic system during diabetes drives vascular and neuroglial dysfunction in DR.