Cell Atlas of The Human Fovea and Peripheral Retina

Wenjun Yan,Joshua R Sanes,Aviv Regev,Tavé Van Zyl,Karthik Shekhar,Yi-Rong Peng,Dejan Juric

doi:10.1038/s41598-020-66092-9

Abstract

Most irreversible blindness results from retinal disease. To advance our understanding of the etiology of blinding diseases, we used single-cell RNA-sequencing (scRNA-seq) to analyze the transcriptomes of ~85,000 cells from the fovea and peripheral retina of seven adult human donors. Utilizing computational methods, we identified 58 cell types within 6 classes: photoreceptor, horizontal, bipolar, amacrine, retinal ganglion and non-neuronal cells. Nearly all types are shared between the two retinal regions, but there are notable differences in gene expression and proportions between foveal and peripheral cohorts of shared types. We then used the human retinal atlas to map expression of 636 genes implicated as causes of or risk factors for blinding diseases. Many are expressed in striking cell class-, type-, or region-specific patterns. Finally, we compared gene expression signatures of cell types between human and the cynomolgus macaque monkey, Macaca fascicularis. We show that over 90% of human types correspond transcriptomically to those previously identified in macaque, and that expression of disease-related genes is largely conserved between the two species. These results validate the use of the macaque for modeling blinding disease, and provide a foundation for investigating molecular mechanisms underlying visual processing.

Highlights

The three leading causes of irreversible blindness can be classified as neurodegenerative retinal diseases: age-related macular degeneration, glaucoma and diabetic retinopathy; photoreceptors are lost in age-related macular degeneration and diabetic retinopathy, and retinal ganglion cells (RGCs) are lost in glaucoma[1,2,3]
From 55,736 foveal and 29,246 peripheral retinal cells, we identified 58 cell types
We used the cell atlas to compare fovea with peripheral retina, and human with macaque retinal cell types

Summary

Introduction

The three leading causes of irreversible blindness can be classified as neurodegenerative retinal diseases: age-related macular degeneration, glaucoma and diabetic retinopathy; photoreceptors are lost in age-related macular degeneration and diabetic retinopathy, and retinal ganglion cells (RGCs) are lost in glaucoma[1,2,3]. One main obstacle to gaining such understanding is lack of knowledge about where the implicated genes are expressed; lacking such information, it is difficult to determine mechanisms by which they affect visual function Another is that substantial differences in structure and gene expression between human and rodent retina have made it difficult to study these genes in animal models. By analyzing a total of 84,982 single cell transcriptomes, we identified 58 cell types in human fovea and 57 types in peripheral retina, most of which were shared between the two regions For many of these types, we documented substantial regional differences in gene expression and proportions. We show that many of the genes queried are selectively expressed in particular retinal cell classes, in particular cell types within a class, or in foveal or peripheral cohorts of shared types These results provide new insights into mechanisms underlying retinal disease

Methods

Results

Conclusion