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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 a model of type 2 diabetes, induced in leptin receptor\u2013deficient (db\/db) and control db\/m mice, with the aim of elucidating the factors mediating the pathogenesis of DR. We identified 11 cell types and determined cell-type-specific expression of DR-associated loci via genome-wide association study (GWAS)-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 M\u00fcller 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.<\/jats:p>","DOI":"10.2337\/db20-0839","type":"journal-article","created":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T18:35:25Z","timestamp":1614969325000},"page":"1185-1197","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":50,"title":["Pathogenesis Study Based on High-Throughput Single-Cell Sequencing Analysis Reveals Novel Transcriptional Landscape and Heterogeneity of Retinal Cells in Type 2 Diabetic Mice"],"prefix":"10.2337","volume":"70","author":[{"given":"Tian","family":"Niu","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine; National Clinical Research Center for Eye Diseases; Shanghai Key Laboratory of Ocular Fundus 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