Journal Article

Interplay between Müller cells and microglia aggravates retinal inflammatory response in experimental glaucoma

Wang, Zhongfeng, Xu, Meng-Xi, Zhou, Han, Li, Fang, Miao, Yanying, Zhao, Guo-Li, Yang, Xiong-Li, Lei, Bo, Hu, Xin

2021

Overview

Background Glaucoma, the leading cause of irreversible blindness, is a retinal neurodegenerative disease, which results from progressive apoptotic death of retinal ganglion cells (RGCs). Although the mechanisms underlying RGC apoptosis in glaucoma are extremely complicated, an abnormal cross-talk between retinal glial cells and RGCs is generally thought to be involved. However, how interaction of Müller cells and microglia, two types of glial cells, contributes to RGC injury is largely unknown. Methods A mouse chronic ocular hypertension (COH) experimental glaucoma model was produced. Western blotting, immunofluorescence, quantitative real-time polymerase chain reaction (q-PCR), transwell co-culture of glial cells, flow cytometry assay, ELISA, Ca 2+ image, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) techniques were employed to investigate the interaction of Müller cells and microglia, and its underlying mechanisms in COH retina. Results We first showed that Müller cell activation in mice with COH induced microglia activation through the ATP/P2X7 receptor pathway. The activation of microglia resulted in a significant increase in mRNA and protein levels of pro-inflammatory factors, such as tumor necrosis factor-α and interleukin-6. These inflammatory factors in turn caused the up-regulation of mRNA expression of pro-inflammatory factors in Müller cells through a positive feedback manner. Conclusions These findings provide robust evidence, for the first time, that retinal inflammatory response may be aggravated by an interplay between activated two types of glial cells. These results also suggest that to reduce the interplay between Müller cells and microglia could be a potential effective strategy for preventing the loss of RGCs in glaucoma.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Activation / Adenosine Triphosphate - physiology / Animals / Antibodies / Apoptosis / ATP/P2X7 receptor / Biomedical and Life Sciences / Biomedicine / Blindness / Cell activation / Cell culture / Cell death / Coculture Techniques / Complications and side effects / Cytokines - metabolism / DNA nucleotidylexotransferase / Enzyme-linked immunosorbent assay / Ependymoglial Cells - pathology / Experiments / Flow cytometry / Gene expression / Glaucoma / Glaucoma - complications / Glial cells / Health aspects / Immunofluorescence / Immunology / Inflammation / Inflammatory response / Interleukin 6 / Laboratory animals / Macrophage Activation / Mice / Mice, Inbred C57BL / Microglia / Microglia - pathology / Mueller cells / Müller cells / Neurobiology / Neurodegenerative diseases / Neurology / Neurosciences / Ocular Hypertension - complications / Polymerase chain reaction / Proteins / Receptors, Purinergic P2X7 / Retina / Retinal ganglion cells / Retinal Ganglion Cells - pathology / Retinitis - etiology / Retinitis - pathology / Signal Transduction / Tumor necrosis factor-TNF / Tumor necrosis factor-α / Western blotting