Researchers discover new drugs for treatment of diabetic retinopathy

In the study, the researchers, identified a molecular target, BCL-xL, present in defective retinal blood vessels. The drug developed by UNITY Biotechnology uses this molecular target to selectively eliminate the defective vessel and thus allow the retina to repair itself. 

"We demonstrate that in contrast to healthy blood vessels, pathological vessels engage pathways of cellular senescence. Senescent (p16INK4A-expressing) cells accumulate in retinas of patients with diabetic retinopathy and during peak destructive neovascularization in a mouse model of retinopathy," wrote the authors.

"Using either genetic approaches that clear p16INK4A-expressing cells or small molecule inhibitors of the anti-apoptotic protein BCL-xL, we show that senolysis suppresses pathological angiogenesis."

According to the study, BCL-xL inhibitor UBX1967 eliminates senescent cells and suppresses neovascularization

"With a single injection," he added, "it would potentially be possible to eliminate groups of cells that contribute to diabetic eye disease, which affects some 750,000 Canadians and is the leading cause of blindness in working-age adults," said Sapieha, a professor in UdeM's Department of Ophthalmology and director of MRH-RC's Neurovascular Eye Disease Research Unit.

"These findings provide mechanistic evidence supporting the development of BCL-xL inhibitors as potential treatments for neovascular retinal disease," concluded the authors.

The study titled, "Pathological angiogenesis in retinopathy engages cellular senescence and is amenable to therapeutic elimination via BCL-xL inhibition," is published in the journal Cell Metabolism.

DOI: https://www.sciencedirect.com/science/article/abs/pii/S1550413121000115