Human iPSC-and Primary-Retinal Pigment Epithelial Cells for Modeling Age-Related Macular Degeneration

Cody R Fisher; Mara C. Ebeling; Zhaohui Geng; Rebecca J. Kapphahn; Heidi Roehrich; Sandra R. Montezuma; James R. Dutton; Deborah A. Ferrington

doi:10.3390/antiox11040605

Human iPSC-and Primary-Retinal Pigment Epithelial Cells for Modeling Age-Related Macular Degeneration

Cody R Fisher, Mara C. Ebeling, Zhaohui Geng, Rebecca J. Kapphahn, Heidi Roehrich, Sandra R. Montezuma, James R. Dutton, Deborah A. Ferrington

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Abstract

Primary cultures of retinal pigment epithelium (RPE) from human adult donors (haRPE) and induced pluripotent stem cell derived-RPE (iPSC-RPE) are valuable model systems for gaining mechanistic insight and for testing potential therapies for age-related macular degeneration (AMD). This study evaluated the treatment response of haRPE and iPSC-RPE to oxidative stress and potential therapeutics addressing mitochondrial defects. haRPE and iSPC-RPE were derived from donors with or without AMD. Mitochondrial function was measured after treatment with menadione, AICAR, or trehalose and the response to treatment was compared between cell models and by disease status. In a subset of samples, haRPE and iPSC-RPE were generated from the same human donor to make a side-by-side comparison of the two cell models’ response to treatment. Disease-specific responses to all three treatments was observed in the haRPE. In contrast, iPSC-RPE had a similar response to all treatments irrespective of disease status. Analysis of haRPE and iPSC-RPE generated from the same human donor showed a similar response for donors without AMD, but there were significant differences in treatment response between cell models generated from AMD donors. These results support the use of iPSC-RPE and haRPE when investigating AMD mechanisms and new therapeutics but indicates that attention to experimental conditions is required.

Original language	English (US)
Article number	605
Journal	Antioxidants
Volume	11
Issue number	4
DOIs	https://doi.org/10.3390/antiox11040605
State	Published - Apr 2022

Bibliographical note

Funding Information:
This work was supported in part by the National Institutes of Health (NIH) National Eye Institute (NEI) F31-EY031558 (to CRF), T32-EY025187 (to CRF), R01EY026012 (to DAF), and R01EY028554 (to DAF and JRD), NIH National Institute of Aging (NIA) T32-AG029796 (to CRF), Diana Jacobs Kalman/AFAR Scholarships for Research in the Biology of Aging (to CRF), VitreoRetinal Surgery Foundation Fellowship (to CRF), the Elaine and Robert Larson Endowed Vision Chair, the Lindsay Family Foundation, and an anonymous benefactor for AMD research.

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

Age-related macular degeneration
Mitochondria
Oxida-tive stress
Retinal pigment epithelium

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@article{0f18b2a7e11f4652a19a505bc9d14660,

title = "Human iPSC-and Primary-Retinal Pigment Epithelial Cells for Modeling Age-Related Macular Degeneration",

abstract = "Primary cultures of retinal pigment epithelium (RPE) from human adult donors (haRPE) and induced pluripotent stem cell derived-RPE (iPSC-RPE) are valuable model systems for gaining mechanistic insight and for testing potential therapies for age-related macular degeneration (AMD). This study evaluated the treatment response of haRPE and iPSC-RPE to oxidative stress and potential therapeutics addressing mitochondrial defects. haRPE and iSPC-RPE were derived from donors with or without AMD. Mitochondrial function was measured after treatment with menadione, AICAR, or trehalose and the response to treatment was compared between cell models and by disease status. In a subset of samples, haRPE and iPSC-RPE were generated from the same human donor to make a side-by-side comparison of the two cell models{\textquoteright} response to treatment. Disease-specific responses to all three treatments was observed in the haRPE. In contrast, iPSC-RPE had a similar response to all treatments irrespective of disease status. Analysis of haRPE and iPSC-RPE generated from the same human donor showed a similar response for donors without AMD, but there were significant differences in treatment response between cell models generated from AMD donors. These results support the use of iPSC-RPE and haRPE when investigating AMD mechanisms and new therapeutics but indicates that attention to experimental conditions is required.",

keywords = "Age-related macular degeneration, Mitochondria, Oxida-tive stress, Retinal pigment epithelium",

author = "Fisher, {Cody R} and Ebeling, {Mara C.} and Zhaohui Geng and Kapphahn, {Rebecca J.} and Heidi Roehrich and Montezuma, {Sandra R.} and Dutton, {James R.} and Ferrington, {Deborah A.}",

note = "Funding Information: This work was supported in part by the National Institutes of Health (NIH) National Eye Institute (NEI) F31-EY031558 (to CRF), T32-EY025187 (to CRF), R01EY026012 (to DAF), and R01EY028554 (to DAF and JRD), NIH National Institute of Aging (NIA) T32-AG029796 (to CRF), Diana Jacobs Kalman/AFAR Scholarships for Research in the Biology of Aging (to CRF), VitreoRetinal Surgery Foundation Fellowship (to CRF), the Elaine and Robert Larson Endowed Vision Chair, the Lindsay Family Foundation, and an anonymous benefactor for AMD research. Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2022",

month = apr,

doi = "10.3390/antiox11040605",

language = "English (US)",

volume = "11",

journal = "Antioxidants",

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T1 - Human iPSC-and Primary-Retinal Pigment Epithelial Cells for Modeling Age-Related Macular Degeneration

AU - Fisher, Cody R

AU - Ebeling, Mara C.

AU - Geng, Zhaohui

AU - Kapphahn, Rebecca J.

AU - Roehrich, Heidi

AU - Montezuma, Sandra R.

AU - Dutton, James R.

AU - Ferrington, Deborah A.

N1 - Funding Information: This work was supported in part by the National Institutes of Health (NIH) National Eye Institute (NEI) F31-EY031558 (to CRF), T32-EY025187 (to CRF), R01EY026012 (to DAF), and R01EY028554 (to DAF and JRD), NIH National Institute of Aging (NIA) T32-AG029796 (to CRF), Diana Jacobs Kalman/AFAR Scholarships for Research in the Biology of Aging (to CRF), VitreoRetinal Surgery Foundation Fellowship (to CRF), the Elaine and Robert Larson Endowed Vision Chair, the Lindsay Family Foundation, and an anonymous benefactor for AMD research. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2022/4

Y1 - 2022/4

N2 - Primary cultures of retinal pigment epithelium (RPE) from human adult donors (haRPE) and induced pluripotent stem cell derived-RPE (iPSC-RPE) are valuable model systems for gaining mechanistic insight and for testing potential therapies for age-related macular degeneration (AMD). This study evaluated the treatment response of haRPE and iPSC-RPE to oxidative stress and potential therapeutics addressing mitochondrial defects. haRPE and iSPC-RPE were derived from donors with or without AMD. Mitochondrial function was measured after treatment with menadione, AICAR, or trehalose and the response to treatment was compared between cell models and by disease status. In a subset of samples, haRPE and iPSC-RPE were generated from the same human donor to make a side-by-side comparison of the two cell models’ response to treatment. Disease-specific responses to all three treatments was observed in the haRPE. In contrast, iPSC-RPE had a similar response to all treatments irrespective of disease status. Analysis of haRPE and iPSC-RPE generated from the same human donor showed a similar response for donors without AMD, but there were significant differences in treatment response between cell models generated from AMD donors. These results support the use of iPSC-RPE and haRPE when investigating AMD mechanisms and new therapeutics but indicates that attention to experimental conditions is required.

AB - Primary cultures of retinal pigment epithelium (RPE) from human adult donors (haRPE) and induced pluripotent stem cell derived-RPE (iPSC-RPE) are valuable model systems for gaining mechanistic insight and for testing potential therapies for age-related macular degeneration (AMD). This study evaluated the treatment response of haRPE and iPSC-RPE to oxidative stress and potential therapeutics addressing mitochondrial defects. haRPE and iSPC-RPE were derived from donors with or without AMD. Mitochondrial function was measured after treatment with menadione, AICAR, or trehalose and the response to treatment was compared between cell models and by disease status. In a subset of samples, haRPE and iPSC-RPE were generated from the same human donor to make a side-by-side comparison of the two cell models’ response to treatment. Disease-specific responses to all three treatments was observed in the haRPE. In contrast, iPSC-RPE had a similar response to all treatments irrespective of disease status. Analysis of haRPE and iPSC-RPE generated from the same human donor showed a similar response for donors without AMD, but there were significant differences in treatment response between cell models generated from AMD donors. These results support the use of iPSC-RPE and haRPE when investigating AMD mechanisms and new therapeutics but indicates that attention to experimental conditions is required.

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KW - Mitochondria

KW - Oxida-tive stress

KW - Retinal pigment epithelium

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ER -

Human iPSC-and Primary-Retinal Pigment Epithelial Cells for Modeling Age-Related Macular Degeneration

Abstract

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