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Lucian Del Priore, Hui Cai, Jie Gong, Laura Abriola, Mark Anthony Fields; Synthetic compound MAF20170220-4 Protects Human Retinal Pigment Epithelial Cells from Oxidative Stress-induced Cell Death. Invest. Ophthalmol. Vis. Sci. 2018;59(9):768.
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Dysfunction and eventual loss of retinal pigment epithelial cells is a hallmark of the pathophysiology of atrophic age-related macular degeneration (AMD). Treatments that slow or retard the development of atrophic AMD would be of value. Herein, we investigated the effects of a synthetic compound, maf20170220-4, on retinal pigment epithelial (RPE) cell survival after oxidative stress-induced cell death.
Human ARPE-19 or human induced pluripotent stem cell-derived (iPSC-derived RPE) cells were treated with tert -butyl hydroperoxide (TBHP, 500 µM) to induce cell death in the presence (0.8µM) or absence of synthetic compound maf20170220-4. Protective effects of synthetic compound maf20170220-4 was measured by cell viability. Reverse transcription polymerase chain reaction (RT-PCR) was used to measure gene expression in RPE cells treated with 500 µM of TBHP in the presence (0.8µM) or absence of synthetic compound maf20170220-4. Mitochondrial function was measured using the Seahorse XF96 analyzer in cells treated with 500 µM TBHP and 0.8µM synthetic compound maf20170220-4. UV-B light damage was induced by ultraviolet B (UV-B) light treatment (1200mJ/cm2) on RPE cells in the presence (0.8µM) or absence of synthetic compound maf20170220-4.
Synthetic compound maf20170220-4 reduced the death of human RPE cells from oxidative stress-induced cell death by at least 67 % (p < 0.01). Treatment with TBHP and synthetic compound maf20170220-4 altered the expression of multiple genes related to oxidative stress such as glutathione peroxidase family gene-1 and -3 (GPX-1 and -3) and apoptosis Bcl-2-associated X protein (BAX) and caspase family gene-8 (CASP-8) in human RPE cells. Synthetic compound maf20170220-4 improved mitochondrial function after oxidative stress-induced cell death in RPE cells as measured by basal and maximal oxygen consumption rate (OCR), spare capacity, and ATP production at least by 2-folds (P < 0.05), and protected human RPE cells from UV-B light damage.
Synthetic compound maf20170220-4 protects RPE cells from oxidative stress-induced cell death and UV-B light damage as well as improves mitochondrial respiration. Our data suggest that synthetic compound maf20170220-4 may be a potential treatment for retinal degenerations, including AMD.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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