July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
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
Author Affiliations & Notes
  • Jie Gong
    Ophthalmology, Yale University, New Haven, Connecticut, United States
  • Huey Cai
    Ophthalmology, Yale University, New Haven, Connecticut, United States
  • Mark Anthony Fields
    Ophthalmology, Yale University, New Haven, Connecticut, United States
  • Lucian V Del Priore
    Ophthalmology, Yale University, New Haven, Connecticut, United States
  • Footnotes
    Commercial Relationships   Jie Gong, None; Huey Cai, None; Mark Fields, None; Lucian Del Priore, None
  • Footnotes
    Support  RPB Research Prevent Blindness
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 1223. doi:https://doi.org/
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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. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : 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.

Methods : 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.

Results : 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.

Conclusions : 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

Basal respiration and ATP production in AMD patients and Normal controls

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