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Pathogenesis Study Based on High Throughput Single-Cell Sequencing Analysis Reveals Novel Transcriptional Landscape and Heterogeneity of Retinal Cells in Type 2 Diabetic Mice

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posted on 05.03.2021, 22:27 by Tian Niu, Junwei Fang, Xin Shi, Mengya Zhao, Xindan Xing, Yihan Wang, Shaopin Zhu, Kun Liu
Diabetic retinopathy (DR) is the leading cause of acquired blindness in middle-aged people. The complex pathology of DR is difficult to dissect, given the convoluted cytoarchitecture of the retina. Here, we performed single-cell RNA sequencing (scRNA-seq) of retina from type 2 diabetic model induced in leptin receptor-deficient (db/db) and control db/m mice with the aim of elucidating the factors mediating the pathogenesis of DR. We identified eleven cell types and determined cell type-specific expression of DR-associated loci via genome-wide association study-based enrichment analysis. DR also impacted cell type-specific genes and altered cell-cell communication. Based on the scRNA-seq results, retinaldehyde-binding protein 1 (RLBP1) was investigated as a promising therapeutic target for DR. Retinal RLBP1 expression was decreased in diabetes, and its overexpression in Müller glia mitigated DR-associated neurovascular degeneration. These data provide a detailed analysis of the retina under diabetic and normal conditions, revealing new insights into pathogenic factors that may be targeted to treat DR and related dysfunctions.

Funding

This work was supported by grants from the National Key R&D Program of China (Grant Nos. 2016YFC0904800, 2019YFC0840607); the National Science and Technology Major Project of China (Grant No. 2017ZX09304010); National Natural Science Foundation of China (81870667 and 81800799); the Shanghai Medical Excellent Discipline Leader Program (Grant No. 2017BR056); and the Shanghai Municipal Education Commission–Gaofeng Clinical Medicine Grant Support Program (Grant No. 20161426).

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