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Single-cell transcriptomics of the human retinal pigment epithelium and choroid in health and macular degeneration.
Proc Natl Acad Sci U S A. 2019 11 26; 116(48):24100-24107.PN

Abstract

The human retinal pigment epithelium (RPE) and choroid are complex tissues that provide crucial support to the retina. Disease affecting either of these supportive tissues can lead to irreversible blindness in the setting of age-related macular degeneration. In this study, single-cell RNA sequencing was performed on macular and peripheral regions of RPE-choroid from 7 human donor eyes in 2 independent experiments. In the first experiment, total RPE/choroid preparations were evaluated and expression profiles specific to RPE and major choroidal cell populations were identified. As choroidal endothelial cells represent a minority of the total RPE/choroidal cell population but are strongly implicated in age-related macular degeneration (AMD) pathogenesis, a second single-cell RNA-sequencing experiment was performed using endothelial cells enriched by magnetic separation. In this second study, we identified gene expression signatures along the choroidal vascular tree, classifying the transcriptome of human choriocapillaris, arterial, and venous endothelial cells. We found that the choriocapillaris highly and specifically expresses the regulator of cell cycle gene (RGCC), a gene that responds to complement activation and induces apoptosis in endothelial cells. In addition, RGCC was the most up-regulated choriocapillaris gene in a donor diagnosed with AMD. These results provide a characterization of the human RPE and choriocapillaris transcriptome, offering potential insight into the mechanisms of choriocapillaris response to complement injury and choroidal vascular disease in age-related macular degeneration.

Authors+Show Affiliations

Department of Ophthalmology and Visual Sciences, The University of Iowa Carver College of Medicine, Iowa City, IA 52242. Institute for Vision Research, The University of Iowa, Iowa City, IA 52242.Department of Ophthalmology and Visual Sciences, The University of Iowa Carver College of Medicine, Iowa City, IA 52242. Institute for Vision Research, The University of Iowa, Iowa City, IA 52242.Department of Ophthalmology and Visual Sciences, The University of Iowa Carver College of Medicine, Iowa City, IA 52242. Institute for Vision Research, The University of Iowa, Iowa City, IA 52242.Department of Ophthalmology and Visual Sciences, The University of Iowa Carver College of Medicine, Iowa City, IA 52242. Institute for Vision Research, The University of Iowa, Iowa City, IA 52242.Department of Ophthalmology and Visual Sciences, The University of Iowa Carver College of Medicine, Iowa City, IA 52242. Institute for Vision Research, The University of Iowa, Iowa City, IA 52242.Department of Ophthalmology and Visual Sciences, The University of Iowa Carver College of Medicine, Iowa City, IA 52242. Institute for Vision Research, The University of Iowa, Iowa City, IA 52242.Department of Ophthalmology and Visual Sciences, The University of Iowa Carver College of Medicine, Iowa City, IA 52242. Institute for Vision Research, The University of Iowa, Iowa City, IA 52242.Department of Ophthalmology and Visual Sciences, The University of Iowa Carver College of Medicine, Iowa City, IA 52242. Institute for Vision Research, The University of Iowa, Iowa City, IA 52242.Department of Ophthalmology and Visual Sciences, The University of Iowa Carver College of Medicine, Iowa City, IA 52242; mullinsrf@gmail.com. Institute for Vision Research, The University of Iowa, Iowa City, IA 52242.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

31712411

Citation

Voigt, Andrew P., et al. "Single-cell Transcriptomics of the Human Retinal Pigment Epithelium and Choroid in Health and Macular Degeneration." Proceedings of the National Academy of Sciences of the United States of America, vol. 116, no. 48, 2019, pp. 24100-24107.
Voigt AP, Mulfaul K, Mullin NK, et al. Single-cell transcriptomics of the human retinal pigment epithelium and choroid in health and macular degeneration. Proc Natl Acad Sci U S A. 2019;116(48):24100-24107.
Voigt, A. P., Mulfaul, K., Mullin, N. K., Flamme-Wiese, M. J., Giacalone, J. C., Stone, E. M., Tucker, B. A., Scheetz, T. E., & Mullins, R. F. (2019). Single-cell transcriptomics of the human retinal pigment epithelium and choroid in health and macular degeneration. Proceedings of the National Academy of Sciences of the United States of America, 116(48), 24100-24107. https://doi.org/10.1073/pnas.1914143116
Voigt AP, et al. Single-cell Transcriptomics of the Human Retinal Pigment Epithelium and Choroid in Health and Macular Degeneration. Proc Natl Acad Sci U S A. 2019 11 26;116(48):24100-24107. PubMed PMID: 31712411.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Single-cell transcriptomics of the human retinal pigment epithelium and choroid in health and macular degeneration. AU - Voigt,Andrew P, AU - Mulfaul,Kelly, AU - Mullin,Nathaniel K, AU - Flamme-Wiese,Miles J, AU - Giacalone,Joseph C, AU - Stone,Edwin M, AU - Tucker,Budd A, AU - Scheetz,Todd E, AU - Mullins,Robert F, Y1 - 2019/11/11/ PY - 2019/11/13/pubmed PY - 2020/4/23/medline PY - 2019/11/13/entrez KW - age-related macular degeneration KW - choriocapillaris KW - choroid KW - single cell SP - 24100 EP - 24107 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc Natl Acad Sci U S A VL - 116 IS - 48 N2 - The human retinal pigment epithelium (RPE) and choroid are complex tissues that provide crucial support to the retina. Disease affecting either of these supportive tissues can lead to irreversible blindness in the setting of age-related macular degeneration. In this study, single-cell RNA sequencing was performed on macular and peripheral regions of RPE-choroid from 7 human donor eyes in 2 independent experiments. In the first experiment, total RPE/choroid preparations were evaluated and expression profiles specific to RPE and major choroidal cell populations were identified. As choroidal endothelial cells represent a minority of the total RPE/choroidal cell population but are strongly implicated in age-related macular degeneration (AMD) pathogenesis, a second single-cell RNA-sequencing experiment was performed using endothelial cells enriched by magnetic separation. In this second study, we identified gene expression signatures along the choroidal vascular tree, classifying the transcriptome of human choriocapillaris, arterial, and venous endothelial cells. We found that the choriocapillaris highly and specifically expresses the regulator of cell cycle gene (RGCC), a gene that responds to complement activation and induces apoptosis in endothelial cells. In addition, RGCC was the most up-regulated choriocapillaris gene in a donor diagnosed with AMD. These results provide a characterization of the human RPE and choriocapillaris transcriptome, offering potential insight into the mechanisms of choriocapillaris response to complement injury and choroidal vascular disease in age-related macular degeneration. SN - 1091-6490 UR - https://www.unboundmedicine.com/medline/citation/31712411/Single_cell_transcriptomics_of_the_human_retinal_pigment_epithelium_and_choroid_in_health_and_macular_degeneration_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=31712411 DB - PRIME DP - Unbound Medicine ER -