Single-Cell Transcriptome Analysis of the Retina During the Development of Normal Tension Glaucoma in Mice

Glaucoma is characterized by the progressive degeneration of retinal ganglion cells (RGCs), the pathogenesis of which is still unknown. Many studies have reported that retinal glial cells play an important role in neuron degeneration, but the underlying mechanisms are not well defined. Systematic analysis at the single-cell level is crucial for better understanding the molecular alterations in major retinal cell types and the interactions between glial cells and RGCs during disease progression. Here, we performed single-cell RNA sequencing (scRNA-seq) on OPTN E50K mutant mice, an in vivo model of normal tension glaucoma (NTG), of different ages and analyzed them by bioinformatics methods to obtain a complete gene expression profile of retinal cells in NTG. We identified the transcriptional signatures of RGCs and changes in their cellular interactions with glial cells during NTG development. Microglia were initially reactive in the early stage of NTG and progressively increased TNF-α expression with age, contributing to retinal degeneration, in which the CD74-MIF pathway played an important role. In addition, Müller cells interacted with microglia and became reactive in NTG. Our study provides a detailed analysis of RGCs and retinal glial cells and enhances the understanding of the mechanism of optic nerve damage during NTG progression, suggesting promising new targets for diagnostic and future therapeutic strategies.