Oxygen and light signaling in healthy and diabetic photoreceptors

Funding: University of Utah Seed Grant and Diabetes Research Connection grants to Dr. Silke Becker.

Related publications:

Rod phototransduction and light signal transmission during type 2 diabetes. Becker, Carroll and Vinberg, 2020, BMJ Open Diabetes Res Care

Diabetic photoreceptors: Mechanisms underlying changes in structure and function. Becker, Carroll and Vinberg, 2020, Visual Neuroscience

Problem/question: Diabetic retinopathy is one of the main complications in patients with diabetes and the most common reason for blindness in the working-age population in the USA. Traditionally diabetic retinopathy has been diagnosed by changes to retinal blood vessels. Recently it has been discovered, however, that the function of photoreceptors is actually disrupted before these vascular changes occur and it is possible that this may drive the development of diabetic retinopathy. In this project we try to understand why and how photoreceptors are affected this early in the disease.

Hypoxia (or lack of oxygen) is one of the main factors driving retinal disease in diabetes. We study whether this is also the reason why photoreceptors function poorly in the diabetic retina and how it affects other cells in the retina. Understanding the early pathological changes in diabetic retinopathy may help us develop ways to diagnose and treat the disease early before clinical damage has occurred.

Approach: We use mice that develop diabetes, which allows us to mimic changes by diabetes in the human retina. By combining in vivo and ex vivo ERG, we can distinguish between functional changes that are caused by direct damage to photoreceptors versus systemic effects that indirectly affect the retina. Ex vivo ERG also allows us to alter the environment that the retina is exposed to and thus mimic changes in the diabetic animal. We use this approach to change the oxygen concentration that the retina is exposed to and monitor changes in the function of retinal cells. These studies are also accompanied by experiments from donor human eyes from healthy and diabetic donors.