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Download fileSingle-cell Transcriptomics Reveals Novel Role of Microglia in Fibrovascular Membrane of Proliferative Diabetic Retinopathy
figure
posted on 2022-01-21, 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 LiuVitreous
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.