Abstract
Presentation Description :
Several studies have implicated the complement system in the development of vascular damage and progression of diabetic retinopathy. There is a link between membrane attack complex (MAC) deposition in the retina and the progression of DR. Extracellular vesicles (EVs), small vesicles that are secreted into the extracellular environment, have a cargo of complement proteins in plasma, suggesting that they can participate in causing the vascular damage associated with DR. We demonstrate that IgG-laden EVs in plasma activate the classical complement pathway and that the quantity of these EVs is increased in diabetes. Moreover, EVs in Streptozotocin (STZ)-induced rat diabetic plasma results in MAC deposition and cytolytic damage in human retinal endothelial cells (HRECs). Removal of the plasma EVs reduced the MAC deposition and abrogated cytolytic damage seen in HRECs. Similarly, lack of IgG in EVs in diabetic mice results in a reduction in retinal vascular damage in STZ induced mouse model.
Together, the results of this study demonstrate that complement activation by IgG-laden EVs in plasma could lead to MAC deposition and contribute to endothelium damage and progression of DR.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.