Deciphering Primate Retinal Aging at Single-Cell Resolution

The retina is a light-sensitive highly-organized tissue, which is vulnerable to aging and age-related retinal diseases. However, the effects of aging on retinal cell types including those present in neural retina and retinal pigment epithelium (RPE), as well as cell types in choroid layer remain largely unknown. Here, we established the single-cell transcriptomic atlas of the retina and adjacent choroid in young and aged non-human primates (NHPs), identifying 15 cell types with distinct gene expression signatures and finding several novel markers. Our analysis reveals that oxidative stress is a major aging feature of the cells in the neural retinal layer, whereas an enhanced inflammatory response is that of RPE and choroidal cells. We also found that the RPE cell is the cell type most susceptible to aging in retina, as evidenced by the decreased cell density as well as the highest numbers of differentially expressed genes overlapping with genes underlying aging and aging-related retinal diseases, along with aberrant cell-cell interactions with its two adjacent layers. Altogether, our study provides the roadmap for understanding retinal aging in a NHP model at single-cell resolution, enabling the identification of new diagnostic biomarkers and potential therapeutic targets for age-related human retinal disorders. Overall design: We collected 7,461 single cells from the whole retinas of 8 young and 8 aged monkeys and performed single-cell RNA-seq sequencing. [Correspondences between file labels and monkey individuals] CE01: YF1, CE07: YF2, CE08: YF3, CE14: YF4 CE04: YM1, CE05: YM2, CE06: YM3, CE15: YM4 CE09: OF1, CE10: OF2, CE13: OF3, CE16: OF4 CE03: OM1, CE11: OM2, CE12: OM3, CE17: OM4