Protecting Retinal Neurons from Diabetes

Diabetic retinopathy (DR) is a common and sightthreatening disease driven largely by tissue inflammation and deterioration of the nerve cells of the retina. While therapies like anti-VEGF injections can help slow the damage in the later stages of DR, new strategies are needed to intervene earlier in the disease process, protecting the retina before irreparable harm is done.

Biomedical researcher Patrice Fort, Ph.D., M.S., has been at the forefront of investigating targets for retinal neuroprotection. For more than a decade, the Fort lab at Kellogg has pursued the potentially protective role of the protein αA-crystallin.

First described in the lens, Dr. Fort’s team has also demonstrated that αA-crystallin/HspB4 plays a protective role in the retina, guarding neurons from the stressors associated with diabetes. They have also shown that one way this protein protects is by changing the environment that promotes inflammation. However, their studies have also demonstrated that, over time, diabetes weakens those protective effects.

“We believe that a specific modification of the protein—called phosphorylation—is key to αA-crystallin’s ability to protect retinal neurons and modulate inflammation,” explains Dr. Fort. “But the mechanisms regulating this process are unknown.”

Dr. Fort has been awarded an NIH R01 grant to close that knowledge gap.

His project has two aims. The first is to identify the key proteins that regulate the phosphorylation of αA-crystallin and describe how they work. The second is to apply the findings from previous studies to demonstrate the potential of using this protective mechanism as a novel treatment option for diabetes complication.

“Using retina cells in culture, we’ve shown that an enhanced form of αA-crystallin is highly protective,” he explains. “The next step is to find out whether it can protect the whole retina from conditions associated with diabetes—in the case of this study, reduced blood flow.”

The long term goal is to design treatments that harness the protective powers of this protein to control or prevent DR.

Header image caption: Patrice Ford, Ph.D.