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Single-cell Transcriptomics Reveals Novel Role of Microglia in Fibrovascular Membrane of Proliferative Diabetic Retinopathy

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posted on 21.01.2022, 17:05 authored by Zizhong Hu, Xiying Mao, Mingkang Chen, Xinjing Wu, Tianye Zhu, Yu Liu, Zhengyu Zhang, Wen Fan, Ping Xie, Songtao Yuan, Qinghuai Liu
Vitreous fibrovascular membranes (FVMs), the hallmark of proliferative diabetic retinopathy (PDR), cause retinal hemorrhage, detachment and eventually blindness. However, little is known about the pathophysiology of FVM. In this study, we employed single-cell RNA sequencing on surgically harvested PDR-FVMs and generated a comprehensive cell atlas of FVM. A total of 8 cellular compositions were identified, with microglia as the major cell population. We identified a GPNMB+ subpopulation of microglia, which presented both profibrotic and fibrogenic properties. Pseudotime analysis further revealed the profibrotic microglia was uniquely differentiated from retina-resident microglia and expanded in PDR setting. Ligand-receptor interactions between the profibrotic microglia and cytokines upregulated in PDR vitreous implicated the involvement of several pathways, including CCR5, IFNGR1 and CD44 signaling, in the microglial activation within PDR microenvironment. Collectively, our description of the novel microglia phenotypes in PDR-FVM may offer new insight into the cellular and molecular mechanism underlying the pathogenesis of DR, as well as potential signaling pathways amenable to disease-specific intervention.

Funding

This study was supported by the National Key Research and Development Program of China (2017YFA0104100 to Q.L., and 2017YFA0104103 to S.Y.); the National Natural Science Foundation of China (81970821 to Q.L., 81900875 to Z.H., and 81870694 to S.Y.); the Special-funded Program on National Key Scientific Instruments and Equipment Development (12027808 to Z.H.); the Key Research and Development Program of Jiangsu Province (BE2018131 to S.Y.); the Natural Science Foundation of Jiangsu Province (BK20191059 to Z.H.);

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