Abstract
ABSTRACTThe human retina is a complex neural tissue that detects light and sends visual information to the brain. However, the molecular and cellular processes that underlie aging primate retina remain unclear. Here, we provide a comprehensive transcriptomic atlas based on 119 520 single cells of the foveal and peripheral retina of humans and macaques covering different ages. The molecular features of retinal cells differed between the two species, suggesting distinct regional and species specializations of the human and macaque retinae. In addition, human retinal aging occurred in a region- and cell-type-specific manner. Aging of human retina exhibited a foveal to peripheral gradient. MYO9A− rods and a horizontal cell subtype were greatly reduced in aging retina, indicating their vulnerability to aging. Moreover, we generated a dataset showing the cell-type- and region-specific gene expression associated with 55 types of human retinal disease, which provides a foundation to understanding of the molecular and cellular mechanisms underlying human retinal diseases. Such datasets are valuable to understanding of the molecular characteristics of primate retina, as well as molecular regulation of aging progression and related diseases.
Highlights
The human retina is a specialized light-sensitive tissue of neurons, glia, and nourishing blood vessels [1,2,3]
Single-cell transcriptomes of primate retina We collected single-cell transcriptomic profiles of 119,520 cells, including 38,558 from six healthy human samples and 80,962 from five macaque samples (Supplementary Table 1), which covered progressive retinal aging, using dropletbased scRNA-seq (10x Genomics platform)
Astrocytes were not detected in the macaque retina (Fig. 1c, Supplementary Fig. 1f-g), consistent with previous scRNA-seq results from M. fascicularis [3]
Summary
The human retina is a specialized light-sensitive tissue of neurons, glia, and nourishing blood vessels [1,2,3]. Different cell types in the retina, including rod and cone photoreceptors as well as bipolar (BCs), amacrine (ACs), horizontal (HCs), ganglion (GCs) and glial cells, are packed together into a tightly organized network that converts incoming light into electrochemical signals, which are relayed to the brain for visual formation [1]. In addition to this complexity, primates, including humans and monkeys, possess a specialized fovea, which is absent in rodent models. Multiple analyses in primates have demonstrated the regionspecific retinal transcriptomes in developing and adult foveal and peripheral retina, suggesting distinct transcriptional regulations in the two regions [3, 9,10,11,12,13,14]
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