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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 2021-03-05, 22:27 authored by Tian Niu, Junwei Fang, Xin Shi, Mengya Zhao, Xindan Xing, Yihan Wang, Shaopin Zhu, Kun LiuDiabetic 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.