September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Modulation of photoreceptor outer segment phagocytosis and degradation by environmental stressors in an hiPSC-derived model system.
Author Affiliations & Notes
  • Sonal Dalvi
    Department of Ophthalmology and Biomedical Genetics, University of Rochester, Rochester, New York, United States
  • Ali Hashim
    Department of Ophthalmology and Biomedical Genetics, University of Rochester, Rochester, New York, United States
  • Chad Galloway
    Department of Ophthalmology and Biomedical Genetics, University of Rochester, Rochester, New York, United States
  • Leslie MacDonald
    Department of Ophthalmology and Biomedical Genetics, University of Rochester, Rochester, New York, United States
  • Ruchira Singh
    Department of Ophthalmology and Biomedical Genetics, University of Rochester, Rochester, New York, United States
    Center for Visual Science, University of Rochester, Rochester, New York, United States
  • Footnotes
    Commercial Relationships   Sonal Dalvi, None; Ali Hashim, None; Chad Galloway, None; Leslie MacDonald, None; Ruchira Singh, None
  • Footnotes
    Support  Brightfocus Foundation Macular Degeneration Research Grant, David Bryant Trust, Knight Templar Eye Foundation Research Starter Grant, Research to prevent Blindness (Career Development Award, Singh- PI), Research to Prevent Blindness (unrestricted grant, Feldon- PI) Retina Research Foundation Pilot Study Grant, University Research Award (University of Rochester).
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 1145. doi:
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    • Get Citation

      Sonal Dalvi, Ali Hashim, Chad Galloway, Leslie MacDonald, Ruchira Singh; Modulation of photoreceptor outer segment phagocytosis and degradation by environmental stressors in an hiPSC-derived model system.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):1145.

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

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Abstract

Purpose : Macular degenerative diseases are multifactorial, the sum of both genetic as well as environmental factors which often affect the retinal pigment epithelium (RPE) cells. Amongst environmental factors, iron toxicity has been implicated in age related macular degeneration (AMD) while cigarette smoke is the number one preventable factor contributing to AMD. The ability to derive RPE from human inducible pluripotent stem cells (hiPSCs) now allows investigation of the additive effect of environmental factors within the genetic background of macular disease patients. This study utilized hiPSC-RPE cells in culture to evaluate the effect of environmental stressors (iron overload, cigarette smoke) on maculopathy-associated physical and functional attributes of RPE cells.

Methods : Established monolayers of hiPSC-RPE were treated either chronically (1 week –1 month) or acutely (24 h) with exogenous iron (ferric ammonium citrate, FAC) or cigarette smoke extract (CSE). Subsequently, morphologic, gene/protein expression and functional characteristics of hiPSC-RPE-treated with environmental stressors (FAC, CSE) were compared to untreated control hiPSC-RPE.

Results : The expression of genes involved in the pigmentation (TYRP1, SILV) and iron homeostasis (FTH1, SLC40A1) pathway(s) were altered in long-term FAC-treated hiPSC-RPE compared to untreated control hiPSC-RPE. Furthermore, both FAC and CSE treatments affected the rate of photoreceptor outer segment (POS) phagocytosis/degradation in hiPSC-RPE cultures. Interestingly, the effect of FAC and/or CSE was different in RPE cultures that had been chronically stressed with POS compared to RPE cultures without any prior POS exposure.

Conclusions : Two significant contributing factors in the progression of macular degenerative disease, iron toxicity and cigarette smoke, alter an obligate function of RPE, phagocytosis/degradation of POS, in hiPSC derived RPE. In addition, chronic iron supplementation also alters metal ion homeostasis, plausibly contributing to RPE dysfunction in hiPSC-derived cultures. Altogether, our data show that hiPSC-RPE cultures are a suitable platform to study the effect of environmental stressors on RPE physiology and thus may be a suitable tool to dissect the contribution of gene vs. environment in specific eye diseases, like macular degeneration.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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