Abstract
BackgroundGlaucoma, 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.MethodsA 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, Ca2+ 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.ResultsWe 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.ConclusionsThese 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.
Highlights
Glaucoma, the leading cause of irreversible blindness, is a retinal neurodegenerative disease, which results from progressive apoptotic death of retinal ganglion cells (RGCs)
To test whether P2X7 receptor (P2X7R) was involved in microglia activation, we examined effects of brilliant blue G (BBG), an antagonist of P2X7R, on translocator protein (TSPO) expression in microglia in DHPG-injected retinas
The results showed that both MPEP and Brilliant blue G (BBG) significantly reduced the number of transferase dUTP nick end labeling (TUNEL)-positive RGCs (Additional file 1: Fig. S7A, B), indicating that Müller cell activation and ATP/P2X7R-mediated microglia activation contribute to RGC apoptotic death in glaucoma
Summary
The leading cause of irreversible blindness, is a retinal neurodegenerative disease, which results from progressive apoptotic death of retinal ganglion cells (RGCs). The mechanisms underlying RGC apoptosis in glaucoma are extremely complicated, an abnormal cross-talk between retinal glial cells and RGCs is gen‐ erally thought to be involved. The leading cause of irreversible blindness, is characterized by optic nerve degeneration, which results from the apoptotic death of retinal ganglion cells (RGCs). The mechanisms underlying RGC apoptosis in glaucoma are extremely complicated, but an abnormal cross-talk between retinal glial cells and RGCs is generally thought to be involved [1, 2]. Hu et al Journal of Neuroinflammation (2021) 18:303 microglia, two major types of retinal glial cells, are activated and the activation of glial cells is commonly characterized by the so-called “Janus-faced” nature. These data suggest a possibility that appropriate reduction of the interplay between Müller cells and microglia could be an effective way for preventing the loss of RGCs in glaucoma
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