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Jie Gong, Huey Cai, Mark Anthony Fields, Lucian V Del Priore; Decreased ATP production and mitochondrial respiration activity in induced pluripotent stem cell (iPSC)-derived Retinal Pigment Epithelial (RPE) cells from Age-Related Macular degeneration (AMD) patients. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1223.
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Mitochondrial dysfunction in RPE cells has been associated with AMD. Previously, we differentiated iPSCs into RPE cells from AMD patients and non-AMD controls. These RPE cells performed critical functions such as phagocytosis of photoreceptor outer segments, the ability to form tight junctions, and retinol metabolism. Here, we evaluated their mitochondrial functions in iPSC-derived RPE cells from AMD and non-AMD controls.
iPSCs were generated from AMD and age-matched normal patients using mRNA, then iPSCs were differentiated into RPE using an established protocol and analyzed by morphology, immunohistochemistry and confocal microscopy (4 dry AMD and 2 age-matched normal controls). Analysis of mitochondrial function was performed on live cells using XFe96 Extracellular Flux Analyzer.
Human iPSC-derived RPE expressed RPE65, CRALBP and ZO-1. IPSC-RPE from AMD patients displayed decreased mitochondrial respiration and ATP production compared with non-AMD normal controls.For basal respiration, the average of 2 Normal controls was 38.47+7.34 pmol/min, and the average of 4 AMD patients was 15.47+7.56 pmol/min. The average AMD is 40.21% of the average Normal for basal respiration (P<0.001).For ATP production, the average of 2 Normal controls was 35.49+4.81 pmol/min, and the average of 4 AMD patients was 15.01+6.76 pmol/min. The average AMD is 42.29% of the average Normal for ATP production (P<0.001).No significant differences were observed in maximum respiration and spare respiratory capacity in all six patients.
Decreased of mitochondrial basal respiration and ATP production were observed in iPSC-derived RPE from AMD patients. These results suggest that iPSCs from AMD patients may provide a viable disease model to study AMD pathology.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
Basal respiration and ATP production in AMD patients and Normal controls
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