Regulations of Retinal Inflammation: Focusing on Müller Glia

Abstract

Retinal inflammation underlies multiple prevalent retinal diseases. While microglia are one of the most studied cell types regarding retinal inflammation, growing evidence shows that Müller glia play critical roles in the regulation of retinal inflammation. Müller glia express various receptors for cytokines and release cytokines to regulate inflammation. Müller glia are part of the blood-retinal barrier and interact with microglia in the inflammatory responses. The unique metabolic features of Müller glia in the retina makes them vital for retinal homeostasis maintenance, regulating retinal inflammation by lipid metabolism, purine metabolism, iron metabolism, trophic factors, and antioxidants. miRNAs in Müller glia regulate inflammatory responses via different mechanisms and potentially regulate retinal regeneration. Novel therapies are explored targeting Müller glia for inflammatory retinal diseases treatment. Here we review new findings regarding the roles of Müller glia in retinal inflammation and discuss the related novel therapies for retinal diseases.

Keywords: Müller glia; cytokines; miRNA; regeneration; retinal inflammation.

FIGURE 1

Regulations of retinal inflammation from the MG. The body of the MG spans across the retina. The MG interact with the microglia in the inner retina through cytokines paracrine signaling and miRNAs. The main signaling pathways involved include MAPK/ERK, NF-κB, JAK/STAT3 and PPARβ/δ. The MG intake the glutamate released by neurons and convert the neurotoxic glutamate to non-toxic glutamine. The MG take in excessive iron and prevent iron-induced inflammation. The MG express TLRs and recognize antigens after infection, and are capable of phagosome-dependent clearance. The MG can express MHCs and release complements. The endfoot of the MG is crucial part of the inner BRB, regulating angiostasis through pro- and anti-angiogenic factors. BRB, blood-retinal barrier; EC, endothelial cells; EMC, extracellular matrix; MHC, major histocompatibility complex; MG, Müller glia; miRNA, micro-RNA.