Single-cell RNA-sequencing reveals the heterogeneity of microglia in fibrous membrane derived from proliferative diabetic retinopathy and proliferative vitreoretinopathy

Fibrous membrane (FM), the hallmark for proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy (PVR), can cause hemorrhages and retinal detachment, which may lead to blindness if not properly treated. However, little is known about the pathophysiology of FM. In this study, we successfully employed single-cell RNA sequencing on the small-sized vitreous FMs, and generated a comprehensive cell atlas of FMs derived from PVR and PDR. Distinct cell compositions were identified in the FMs, with microglia as the major cell population. Additionally, our analysis revealed a spectrum of microglia activation states with distinct molecular signatures and intercellular interactions in disease-specific microenvironment. This description of microglia phenotypes in the FM of PVR and PDR may offer insight into the activation of microglia in the FM pathogenesis, as well as potential signaling pathways amenable to disease-specific intervention. Overall design: Fibrous membrane samples from one paitient with proliferative vitreoretinopathy and three patients with proliferative diabetic retinopathy were surgically incised and and sequenced using the scFTD-seq protocol.