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Yoon Jeon Kim, Sang A Kim, Jeong A Choi; Restoration of translocator protein dysfunction alleviates oxidative stress induced by A2E in human retinal pigment epithelial cells. Invest. Ophthalmol. Vis. Sci. 2022;63(7):801 – F0360.
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© ARVO (1962-2015); The Authors (2016-present)
We investigated the effects of translocator protein (TSPO) on the functional regulation of retinal pigment epithelium (RPE) using an A2E (N-retinylidene-N-retinylethanolamine) induced cellular stress model, mimicking lipofuscin accumulation in degenerative RPE cells.
We examined A2E-induced changes of TSPO mRNA level in a human RPE cell line (ARPE19). To figure out the function of TSPO in RPE cells, we treated TSPO siRNA for 24 hours and compared their viabilities and oxidative stress levels with the negative control group. Cellular functions following TSPO ligand treatment were investigated.
Four hours after A2E treatment, A2E-exposed ARPE19 exhibited significant induction of oxidative stress and increase in mRNA of TSPO accompanied with intracellular A2E accumulation. Knock-down of TSPO with siRNA exhibited increased intracellular accumulation of A2E and aggravated oxidative stress without significant changes in cell viability. Treatment with TSPO ligand reduced A2E accumulation and restored oxidative stress response.
Our results support the possibility that restoration of TSPO homeostasis may help overcome A2E-induced cellular stress in ARPE19 cells, serving as a potential therapeutic strategy of AMD.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.
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