DZHK researchers led by Professor Ingrid Fleming from the Rhein-Main partner site have identified a lipid mediator that plays a role in the destabilization of endothelial cell-pericyte interactions in the retina to precipitate non-proliferative diabetic retinopathy.
The study reports that the expression of an enzyme, the soluble epoxide hydrolase (sEH), was elevated in retinas from humans and mice with non-proliferative diabetic retinopathy. Mechanistically, the sEH metabolises the fish oil, docosahexaenoic acid to a diol that targets the cell membrane to alter the localization of cholesterol-binding proteins, thereby compromising pericyte-endothelial cell interactions and inter-endothelial cell junctions. Importantly, overexpression of sEH in the retinas of non-diabetic mice resulted in similar vessel abnormalities to those seen in diabetic mice with retinopathy. On the other hand, treating diabetic mice with a specific sEH inhibitor prevented the pericyte loss and vascular permeability, thus identifying a new therapeutic approach for non-proliferative diabetic retinopathy.