Ki-Hong Jang, Young-hoon Kim, Ju-hee Lee and Eunhee Kim
Department of Biological sciences, Chungnam National University
R&D center, Kukje Pharmaceutical Company Limited
Posters & Accepted Abstracts: J Clin Exp Ophthalmol
Degeneration of retinal pigment epithelial (RPE) cells is crucial in the progression of dry age-related macular degeneration (dry-AMD). Here, we investigated the status of autophagy and found that autophagic flux was downregulated in human cultured RPE cells (ARPE-19) upon H2O2. Furthermore, autophagic inhibition sensitized APRE-19 cells to H2O2, implying that protective aspect of autophagy plays a significant role in RPE survival against oxidative stress. Our previous study reported that poly (ADP-ribose) polymerase 1 (PARP1)-dependent necrosis, parthanatos, plays predominant roles in the pathogenesis of dry-AMD (CDDis, 8(1):e2526, 2017). This led us to investigate whether parthanatos process is related to that of the autophagy in RPE cells under oxidative stress. To this end, we examined whether inhibition of PARP1 affects autophagy process in ARPE19 cells. Treatment of PARP1 inhibitor, olaparib, restored autophagic flux and protected ARPE-19 cells upon H2O2. Hence, PARP1 activation accomplishes necrosis of RPE cells via suppression of survival aspect of autophagy upon H2O2. Collectively, our data demonstrate the presence of parthanatos-autophagy crosstalk in the pathogenesis of dry AMD. [This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIP) (NRF-2017M3A9C8021844).].