An Investigation of the GAPDH/Siah1 Pathway in Human Retinal Pericyte Apoptosis

Abstract

Diabetic Retinopathy (DR) is a leading cause of blindness worldwide, and its prevalence is growing. Current therapies for DR address only the later stages of the disease, are invasive and are of limited effectiveness. Retinal pericyte death is an early pathologic feature of DR. Though it has been observed in diabetic patients and in animal models of DR, the cause of pericyte death remains unknown. A novel pro-apoptotic pathway initiated by the interaction between glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the E3 ubiquitin ligase, seven in absentia homolog 1 (Siah1), was identified to play a significant role in human retinal pericyte apoptosis. Inhibition of the GAPDH/Siah1 pro-apoptotic complex blocks diabetes-induced pericyte apoptosis, widely considered a hallmark feature of DR.