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

Autor:	Niu T; 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 Diseases; Shanghai Engineering Center for Visual Science and Photo Medicine; and Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China., Fang J; 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 Diseases; Shanghai Engineering Center for Visual Science and Photo Medicine; and Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China., Shi X; 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 Diseases; Shanghai Engineering Center for Visual Science and Photo Medicine; and Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China., Zhao M; 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 Diseases; Shanghai Engineering Center for Visual Science and Photo Medicine; and Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China., Xing X; 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 Diseases; Shanghai Engineering Center for Visual Science and Photo Medicine; and Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China., Wang Y; 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 Diseases; Shanghai Engineering Center for Visual Science and Photo Medicine; and Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China., Zhu S; 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 Diseases; Shanghai Engineering Center for Visual Science and Photo Medicine; and Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China., Liu K; 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 Diseases; Shanghai Engineering Center for Visual Science and Photo Medicine; and Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China drliukun@sjtu.edu.cn.
Jazyk:	angličtina
Zdroj:	Diabetes [Diabetes] 2021 May; Vol. 70 (5), pp. 1185-1197. Date of Electronic Publication: 2021 Mar 05.
DOI:	10.2337/db20-0839
Abstrakt:	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 a model of type 2 diabetes, 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 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 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. (© 2021 by the American Diabetes Association.)
Databáze:	MEDLINE
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