June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Altered Age Related Macular Degeneration-related Gene Expression in iPSC-derived RPE Cells from AMD vs. non-AMD Individuals
Author Affiliations & Notes
  • Huey Cai
    Ophthalmology & Visual Science, Yale School of Medicine, New Haven, Connecticut, United States
  • Jie Gong
    Ophthalmology & Visual Science, Yale School of Medicine, New Haven, Connecticut, United States
  • Lucian V Del Priore
    Ophthalmology & Visual Science, Yale School of Medicine, New Haven, Connecticut, United States
  • Mark Anthony Fields
    Ophthalmology & Visual Science, Yale School of Medicine, New Haven, Connecticut, United States
  • Footnotes
    Commercial Relationships   Huey Cai None; Jie Gong None; Lucian Del Priore None; Mark Fields None
  • Footnotes
    Support  Alonzo Family Fund
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 3189. doi:
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      Huey Cai, Jie Gong, Lucian V Del Priore, Mark Anthony Fields; Altered Age Related Macular Degeneration-related Gene Expression in iPSC-derived RPE Cells from AMD vs. non-AMD Individuals. Invest. Ophthalmol. Vis. Sci. 2023;64(8):3189.

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

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Abstract

Purpose : We have shown previously that RPE cells derived from age-related macular degeneration (AMD) donors display both a distinct mitochondrial gene expression profile and phenotype compared to age-matched controls. Here, we determine whether the AMD-related gene expression pattern of induced pluripotent stem cell (iPSC)-derived RPE cells from AMD patients differ from age-matched controls.

Methods : iPSCs were generated from fibroblasts isolated from four AMD patients (2 atrophic and 2 exudative) and three age-matched, non-AMD controls. RPE derived from iPSCs were generated using established protocols and analyzed by morphology, cell type specific marker expression, transepithelial resistance (TER), and phagocytosis of rod photoreceptor outer segments. Cells were cultured in standard RPE culture medium for two weeks. DNA microarray which includes 23,000 well annotated genes was conducted on iPSC-derived RPE samples. Altered AMD-related genes were identified and analyzed with corresponding genotypic data.

Results : Differentiated RPE displayed cell-type-specific morphology, markers, TER and phagocytic capacity. AMD-related genes were gathered from published literature. Expression levels of more than 300 AMD-related genes are altered in RPE derived from AMD patients compared to age-matched controls, including CLSTN2 (calsyntenin 2), GSTT2 (glutathione S-transferase theta 2), IGF2BP1 (insulin-like growth factor 2 mRNA binding protein 1) and MMP10 (matrix metallopeptidase 10) compared to non-AMD controls. Additionally, some genotypic alleles display variance on identified altered gene loci from AMD-derived RPE cells. These gene expression changes were not observed at the fibroblast and iPSC level from these individual donors.

Conclusions : Here, we provide evidence that RPE cells differentiated from human iPSC-derived from AMD patients display altered AMD-related gene expression. Further exploration of affected genes and its relation to genotype alleles variances may pave the way for novel treatments for AMD.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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