Abstract
Presentation Description :
Age-related macular degeneration (AMD) is the leading cause of irreversible blindness and visual impairment in the elderly population. One of the significant unsolved challenges of AMD is understanding the mechanism of drusen formation. To overcome this problem, our studies seek to understand how little vesicles, called extracellular vesicles (EVs), secreted by RPE and the retina containing many cellular bioproducts, contribute to drusen formation and AMD progression. EVs are released by all cells and can deliver lipids, proteins, and nucleic acids to nearby and distal cells. The cargo of EVs is related to the nature and physiology of their cell of origin, and any change in cell homeostasis might modify their molecular composition. We provide evidence that drusen-associated proteins are secreted as EVs cargo by RPE in response to AMD stressors. Our recent findings and other studies suggest that in the aged RPE, increased exocytotic activity leads to the release of intracellular proteins via EVs, which potentially contribute to the formation of drusen. Furthermore, we took a critical approach to the enrichment and characterization of EVs from human postmortem retina and RPE. This method maintains the integrity of the EVs and their cargo. It enables researchers to acquire more detailed information about EVs in the eye and explore the role(s) this form of intercellular communication has in healthy eye function and pathogenic conditions such as AMD. Excitingly, due to the EV’s capacity to travel through different biofluids such as blood, tears, and saliva, and since their cargo changes under pathological conditions, EVs could give us the key to diagnosing AMD early and successfully treating it. If we can better understand the origin of drusen, we would be more capable of stopping, preventing, or treating AMD.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.