July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Human retinal progenitor cells (hRPCs) protect age-related macular degeneration (AMD) transmitochondrial ARPE-19 cybrids from cellular damage.
Author Affiliations & Notes
  • Jeffrey Yu
    Ophthalmology, UC Irvine School of Medicine, Long Beach, California, United States
  • Gina Hsiang
    Ophthalmology, UC Irvine School of Medicine, Long Beach, California, United States
  • Kevin Schneider
    Ophthalmology, UC Irvine School of Medicine, Long Beach, California, United States
  • Marilyn Chwa
    Ophthalmology, UC Irvine School of Medicine, Long Beach, California, United States
  • Henry J Klassen
    Ophthalmology, UC Irvine School of Medicine, Long Beach, California, United States
  • Cristina M Kenney
    Ophthalmology, UC Irvine School of Medicine, Long Beach, California, United States
  • Jing Yang
    Ophthalmology, UC Irvine School of Medicine, Long Beach, California, United States
  • Footnotes
    Commercial Relationships   Jeffrey Yu, None; Gina Hsiang, None; Kevin Schneider, None; Marilyn Chwa, None; Henry Klassen, None; Cristina Kenney, None; Jing Yang, None
  • Footnotes
    Support  Funding Supported by Discovery Eye Foundation, Polly and Michael Smith, Iris and B. Gerald Cantor Foundation, Roy and Edith Carver Foundation, Max Factor Family Foundation. Supported by an RPB Unrestricted Grant. Jeffrey Yu holds a Mabel and Arnold Beckman Foundation Fellowship. We acknowledge support from the Institute for Clinical and Translational Science (ICTS) at University of California Irvine.
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 2468. doi:
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    • Get Citation

      Jeffrey Yu, Gina Hsiang, Kevin Schneider, Marilyn Chwa, Henry J Klassen, Cristina M Kenney, Jing Yang; Human retinal progenitor cells (hRPCs) protect age-related macular degeneration (AMD) transmitochondrial ARPE-19 cybrids from cellular damage.. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2468.

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

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Abstract

Purpose : Purpose: Human retinal progenitor cells (hRPCs) have been shown to protect existing photoreceptors and preserve vision in preclinical models of retinal degeneration. We tested the hypothesis that hRPCs would suppress the gene expression changes seen in AMD by utilizing a cell co-culture system consisting of hRPCs and a transmitochondrial cybrid model of AMD.

Methods : Transmitochondrial cybrids containing identical healthy nuclei but mitochondria from different individual AMD patients were created by fusing DNA-deficient ARPE-19 (Rho0) cells with platelets isolated from AMD patients that were clinically well characterized. The transmitochondrial cybrid lines (N=3) were grown with and without the presence of hRPCs using a transwell system. RNA was extracted at 48 hours and reverse transcribed into cDNA. qRT-PCR was performed to assess the expression of apoptosis, autophagy, and ER stress genes. Relative expression was determined using the ΔΔCt method followed by Student’s t-test.

Results : Expression of genes associated with cell damage and death were decreased in the hRPC-treated cells compared to untreated controls (reported as percent expression +/- SEM). Apoptosis genes: BAX (67.4% +/- 1.5%, p=0.0020), CASP7 (68.9% +/- 2.3%, p=0.0054), CASP9 (89.8% +/- 3.0%, p=0.0746). Autophagy genes: ATG5 (82.9% +/- 1.4%, p=0.0065), ATG12 (65.9% +/- 16.6%, p=0.0704), p=.0271), LAMP2 (63.2% +/- 4.5%, p=0.0149), LC3B (86.3% +/- 2.7%, p=0.0378), PARK2 (70.9% +/- 2.8%, p=0.0091). ER stress genes: DDIT3 (45.2% +/- 15.9%[J1] , p=0.0271), XBP1 (70.2% +/- 3.0%, p=0.0101).

Conclusions : Co-culture with hRPCs decreased expression of genes associated with cell damage and death in AMD transmitochondrial cybrids. These results suggest that hRPCs release factors that are protective against the cellular changes involved in AMD pathogenesis.

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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