Cell culture models to study retinal pigment epithelium-related pathogenesis in age-related macular degeneration

Kapil Bharti¹, Anneke I den Hollander², Aparna Lakkaraju³, Debasish Sinha⁴, David S Williams⁵, Silvia C Finnemann⁶, Catherine Bowes-Rickman⁷, Goldis Malek⁸, Patricia A D'Amore⁹

Affiliations

¹ Ocular and Stem Cell Translational Research Section, National Eye Institute, NIH, Bethesda, MD, USA. Electronic address: kapil.bharti@nih.gov.
² Department of Ophthalmology, Radboud University Medical Center, Nijmegen, the Netherlands; AbbVie, Genomics Research Center, Cambridge, MA, USA. Electronic address: anneke.denhollander@abbvie.com.
³ Department of Ophthalmology, School of Medicine, University of California, San Francisco, USA. Electronic address: Aparna.Lakkaraju@ucsf.edu.
⁴ Department of Ophthalmology, Cell Biology and Developmental Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: DEBASISH@pitt.edu.
⁵ Stein Eye Institute, Departments of Ophthalmology and Neurobiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. Electronic address: dswilliams@ucla.edu.
⁶ Center of Cancer, Genetic Diseases, and Gene Regulation, Department of Biological Sciences, Fordham University, Bronx, NY, USA. Electronic address: finnemann@fordham.edu.
⁷ Duke Eye Center, Department of Ophthalmology, Duke University School of Medicine, Durham, NC, USA; Department of Cell Biology, Duke University School of Medicine, Durham, NC, USA. Electronic address: bowes007@duke.edu.
⁸ Duke Eye Center, Department of Ophthalmology, Duke University School of Medicine, Durham, NC, USA; Department of Pathology, Duke University School of Medicine, Durham, NC, USA. Electronic address: gmalek@duke.edu.
⁹ Mass Eye and Ear, Departments of Ophthalmology and Pathology, Harvard Medical School, Boston, MA, USA. Electronic address: patricia_damore@meei.harvard.edu.

PMID: 35835183
PMCID: PMC9444976
DOI: 10.1016/j.exer.2022.109170

Review

Cell culture models to study retinal pigment epithelium-related pathogenesis in age-related macular degeneration

Kapil Bharti et al. Exp Eye Res. 2022 Sep.

. 2022 Sep:222:109170.

doi: 10.1016/j.exer.2022.109170. Epub 2022 Jul 11.

Authors

Kapil Bharti¹, Anneke I den Hollander², Aparna Lakkaraju³, Debasish Sinha⁴, David S Williams⁵, Silvia C Finnemann⁶, Catherine Bowes-Rickman⁷, Goldis Malek⁸, Patricia A D'Amore⁹

Affiliations

¹ Ocular and Stem Cell Translational Research Section, National Eye Institute, NIH, Bethesda, MD, USA. Electronic address: kapil.bharti@nih.gov.
² Department of Ophthalmology, Radboud University Medical Center, Nijmegen, the Netherlands; AbbVie, Genomics Research Center, Cambridge, MA, USA. Electronic address: anneke.denhollander@abbvie.com.
³ Department of Ophthalmology, School of Medicine, University of California, San Francisco, USA. Electronic address: Aparna.Lakkaraju@ucsf.edu.
⁴ Department of Ophthalmology, Cell Biology and Developmental Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: DEBASISH@pitt.edu.
⁵ Stein Eye Institute, Departments of Ophthalmology and Neurobiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. Electronic address: dswilliams@ucla.edu.
⁶ Center of Cancer, Genetic Diseases, and Gene Regulation, Department of Biological Sciences, Fordham University, Bronx, NY, USA. Electronic address: finnemann@fordham.edu.
⁷ Duke Eye Center, Department of Ophthalmology, Duke University School of Medicine, Durham, NC, USA; Department of Cell Biology, Duke University School of Medicine, Durham, NC, USA. Electronic address: bowes007@duke.edu.
⁸ Duke Eye Center, Department of Ophthalmology, Duke University School of Medicine, Durham, NC, USA; Department of Pathology, Duke University School of Medicine, Durham, NC, USA. Electronic address: gmalek@duke.edu.
⁹ Mass Eye and Ear, Departments of Ophthalmology and Pathology, Harvard Medical School, Boston, MA, USA. Electronic address: patricia_damore@meei.harvard.edu.

PMID: 35835183
PMCID: PMC9444976
DOI: 10.1016/j.exer.2022.109170

Abstract

Age-related macular degeneration (AMD) is a disease that affects the macula - the central part of the retina. It is a leading cause of irreversible vision loss in the elderly. AMD onset is marked by the presence of lipid- and protein-rich extracellular deposits beneath the retinal pigment epithelium (RPE), a monolayer of polarized, pigmented epithelial cells located between the photoreceptors and the choroidal blood supply. Progression of AMD to the late nonexudative "dry" stage of AMD, also called geographic atrophy, is linked to progressive loss of areas of the RPE, photoreceptors, and underlying choriocapillaris leading to a severe decline in patients' vision. Differential susceptibility of macular RPE in AMD and the lack of an anatomical macula in most lab animal models has promoted the use of in vitro models of the RPE. In addition, the need for high throughput platforms to test potential therapies has driven the creation and characterization of in vitro model systems that recapitulate morphologic and functional abnormalities associated with human AMD. These models range from spontaneously formed cell line ARPE19, immortalized cell lines such as hTERT-RPE1, RPE-J, and D407, to primary human (fetal or adult) or animal (mouse and pig) RPE cells, and embryonic and induced pluripotent stem cell (iPSC) derived RPE. Hallmark RPE phenotypes, such as cobblestone morphology, pigmentation, and polarization, vary significantly betweendifferent models and culture conditions used in different labs, which would directly impact their usability for investigating different aspects of AMD biology. Here the AMD Disease Models task group of the Ryan Initiative for Macular Research (RIMR) provides a summary of several currently used in vitro RPE models, historical aspects of their development, RPE phenotypes that are attainable in these models, their ability to model different aspects of AMD pathophysiology, and pros/cons for their use in the RPE and AMD fields. In addition, due to the burgeoning use of iPSC derived RPE cells, the critical need for developing standards for differentiating and rigorously characterizing RPE cell appearance, morphology, and function are discussed.

Keywords: ARPE19; Complement system; Organ-on-a-Chip; Primary cells; Retinal pigment epithelium; iPSC-RPE.

Published by Elsevier Ltd.

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Conflict of interest statement

Declaration of competing interest Anneke is currently an employee of AbbVie.

References

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Cell culture models to study retinal pigment epithelium-related pathogenesis in age-related macular degeneration

Affiliations

Cell culture models to study retinal pigment epithelium-related pathogenesis in age-related macular degeneration

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous