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Chun Yang, saeideh shani, Houda Tahiri, Carmen Gagnon, Stéphane Croteau, Pierre Hardy; Extracellular microparticles derived from retinal pigment epithelial cells mediate oxidative damages in the retina. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1688.
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Oxidative stress is a primary contributing factor to early dry age-related macular degeneration (AMD). Oxidative injury to the retina may promote extracellular microparticles (RMPs) released from the retinal pigmented epithelium (RPE). This study was designed to investigate whether RMPs cause RPE cell dysfunction.
RMPs were isolated from human ARPE-19 cells under oxidative stress. The oxidative stress-induced RMPs in vitro and in vivo were characterized using Nanosight and FACS analysis. Fluorescent DiI-labelled RMPs were used to assess uptake into RPE cells. MTT assay and [3H]-thymidine incorporation assay were used to determine cell viability and cell proliferation respectively. Expression of cell cycle genes was analyzed by quantitative RT-PCR and Western blot. The effects of RMPs on RPE cell senescence and phagocytosis were assessed.
Oxidative stress induced EVs released from RPE cells; RMPs constitute over 95% of the EVs. Significantly more RMPs were released from aged RPE cells. RMPs were taken up by RPE cells in a time-dependent manner, however, blockage of CD36 attenuated the uptake process. The decrease of RPE cell viability and cell proliferation by RMPs treatment was associated with an increased expression of cyclin-dependent kinase inhibitors p15 and p21. Moreover, RMPs enhanced senescent and interrupted phagocytic activity in RPE cells.
This study demonstrates that oxidative-induced RMPs produce a strong effect of inducing RPE cell degeneration (a major feature of AMD). These data support the RPE oxidant injury hypothesis in which oxidative stress promotes RPE cell release microparticles and accumulation of RMPs leads to RPE cells dysfunction and consequently accelerating the subretinal deposits. Our finding may uncover a potentially relevant process in the genesis of dry AMD.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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