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Single-Cell RNA Sequencing in Human Retinal Degeneration Reveals Distinct Glial Cell Populations.

ABSTRACT: Degenerative diseases affecting retinal photoreceptor cells have numerous etiologies and clinical presentations. We clinically and molecularly studied the retina of a 70-year-old patient with retinal degeneration attributed to autoimmune retinopathy. The patient was followed for 19 years for progressive peripheral visual field loss and pigmentary changes. Single-cell RNA sequencing was performed on foveal and peripheral retina from this patient and four control patients, and cell-specific gene expression differences were identified between healthy and degenerating retina. Distinct populations of glial cells, including astrocytes and Müller cells, were identified in the tissue from the retinal degeneration patient. The glial cell populations demonstrated an expression profile consistent with reactive gliosis. This report provides evidence that glial cells have a distinct transcriptome in the setting of human retinal degeneration and represents a complementary clinical and molecular investigation of a case of progressive retinal disease.

SUBMITTER: Voigt AP

PROVIDER: S-EPMC7072666 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Single-Cell RNA Sequencing in Human Retinal Degeneration Reveals Distinct Glial Cell Populations.

Voigt Andrew P AP Binkley Elaine E Flamme-Wiese Miles J MJ Zeng Shemin S DeLuca Adam P AP Scheetz Todd E TE Tucker Budd A BA Mullins Robert F RF Stone Edwin M EM

Cells 20200213 2

Degenerative diseases affecting retinal photoreceptor cells have numerous etiologies and clinical presentations. We clinically and molecularly studied the retina of a 70-year-old patient with retinal degeneration attributed to autoimmune retinopathy. The patient was followed for 19 years for progressive peripheral visual field loss and pigmentary changes. Single-cell RNA sequencing was performed on foveal and peripheral retina from this patient and four control patients, and cell-specific gene e ...[more]

PMID: 32069977

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Project description:Purpose: The goals of this study were to identify cell specific expression patterns from a donor with a presumed diagnosis of autoimmune retinopathy (AIR). A particular focus of this study was to identify expression signatures of Müller glia and astrocytes in AIR. Methods: Independent libraries were prepared for foveal and peripheral retina from five human donors in two experiments. Foveal and peripheral samples in donors 1-3 were acquired, analyzed, and uploaded in a previous experiment (GSE130636). In donors 4-5, new reads were acquired from a 2-mm fovea-centered punch and an 8-mm peripheral punch from the inferotemporal region in each donor. Donor 4 had no documented history of retinal disease. Donor 5 was followed for 19 years at the University of Iowa Hospitals and Clinics for progressive visual field loss and pigmentary changes and was given a presumptive diagnosis of autoimmune retinopathy. Foveal and peripheral retinal tissue were gently dissociated in papain for 1.25 hours before cryopreservation. In both experiments, libraries were sequenced on a HiSeq4000. Sequenced reads were mapped to the human genome build hg19 with CellRanger(v3.0.1) and filtered to remove cells likely to be doublets or cells with a high proportion of mitochondrial reads. Libraries from all five donors were aggregated to the same effective sequencing depth, and log-normalization of aggregated reads was performed with Seurat (v2.3.4) using a scale factor of 10,000. Results: A total of 23,429 cells were recovered after filtering with 117,885,744 corresponding reads. A total of 9,801 cells were recovered from the fovea while 13,628 cells were recovered from the periphery. A total of 7,189 cells were recovered from the donor with presumed AIR. In total, 23 clusters were identified and corresponded to all retinal cell types. The proportion of recovered cells was compared between the control (donors 1-4) and AIR (donor 5) patients. In addition, differential expression analysis identified genes enriched in each population of cells originating from the AIR donor. Particular emphasis was given to the expression profiles of glial cells (Müller cells and astrocytes) that originated from the AIR donor. Conclusions: This study provides a complementary clinical and molecular interrogation of the retina in a blinding inflammatory condition. Glial cells from the AIR donor were enriched in genes implicated in reactive gliosis, including ANXA1. Clinical, histologic, and transcriptomic evidence identify the loss of cone and rod photoreceptor cells with relative preservation of inner retinal cell types.

Dataset Information

Single-Cell RNA Sequencing in Human Retinal Degeneration Reveals Distinct Glial Cell Populations.

Publications

Single-Cell RNA Sequencing in Human Retinal Degeneration Reveals Distinct Glial Cell Populations.

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