灵长类视网膜衰老 z-bo 2020-10-23 346

　　The degeneration of retinal function accompanied by aging is one of the main reasons that cause retinal degenerative diseases such as macular degeneration, which in turn leads to visual impairment or loss of the elderly, and seriously affects the quality of life of the elderly. The retina can sense light stimulation and convert it into electrical signals that are transmitted to the visual center of the cerebral cortex through nerves to form vision. The retina has a complex structure, which is mainly divided into the neural retinal layer and the retinal pigment epithelium (RPE) layer. In addition, the choroid closely connected with RPE also plays an important role in nutrition and support to the retina. Due to the high heterogeneity and complexity of the retinal structure, it is difficult for traditional research techniques to accurately reveal the key susceptible cells in the process of retinal degenerative changes, as well as the specific gene change rules of cell types.

　　On October 14, Qu Jing's research group from the Institute of Zoology, Chinese Academy of Sciences, Tang Fuchou's research group, Peking University, and Liu Guanghui's research group from the Institute of Zoology, Chinese Academy of Sciences, published an article in Protein & Cell. The study uses single-cell transcriptome sequencing technology to draw A high-precision single-cell transcriptome map of non-human primate retinal aging was developed, and the gene expression changes in the primate retina and choroidal degeneration process were systematically analyzed.

　　The researchers first obtained the retina and choroid tissues of young and old cynomolgus monkeys, and through a series of morphological analyses, they found that the old retinal tissues showed a decrease in cones, RPE cells, and photoreceptor cells and RPE cells. Changes in the loose structure and increase of lipofuscin in RPE suggest that the key functional cells in the elderly retina have undergone degenerative changes in structure and function. Furthermore, the researchers used the optimized STRT (Single-cell tagged reverse transcription) single-cell transcriptome sequencing technology to systematically identify 15 main cell types, including cones, rod cells, RPE cells, and other retinal cells and Choroid layer cells including fibroblasts and vascular endothelial cells. In addition, a subpopulation of Müller glial cells with neurodevelopmental potential was also identified, and gene expression characteristics specific to the cell type were depicted.

　　Through the analysis of aging-related differentially expressed genes (DEG), the researchers found that the neural retinal layer cells showed the activation of pressure response pathways and the loss of neural signal transduction, while RPE and choroidal layer cells showed increased immuno-inflammatory And the decline of structural support functions. Further studies have shown that RPE cells are one of the most sensitive cell types to aging in the retina: On the one hand, the combined analysis of aging-related DEG and aging and eye disease gene sets shows that the number of aging and disease high-risk genes enriched in RPE is the largest On the other hand, as an important support cell at the junction of the neural retina layer and the choroid layer, RPE cells exhibit abnormal cell-cell interactions during aging, including the upregulation of the immune-inflammatory response pathway between RPE and choroidal cells. Down-regulation of neural communication signals with neural retinal cells.

　　This work has deepened people’s understanding of age-related structural and functional changes in retinal tissue, and analyzed the key susceptible cell types and susceptible molecules of the retina and choroid layer during aging, as well as the changes in the interaction between the retina and choroid layer, as an early warning And the treatment of retinal aging and related diseases provides potential targets for intervention.

　　The research was completed by the Institute of Zoology, Chinese Academy of Sciences, Institute of Stem Cell and Regenerative Medicine Innovation of Chinese Academy of Sciences, Peking University, Beijing Institute of Genomics, Chinese Academy of Sciences, Xuanwu Hospital of Capital Medical University, Peking University Third Hospital and other institutions. The project was funded by the Ministry of Science and Technology, the National Natural Science Foundation of China, the Chinese Academy of Sciences and Beijing.