A review of the role of glial cells in understanding retinal disease

Abstract

Retinal vascular diseases such as diabetic retinopathy and retinopathy of prematurity are major causes of visual loss. Although the focus of a great deal of research has been on the aetiology of vascular growth, it is now emerging that anomalies in other retinal cell types, especially glial cells, occur very early in the course of the disease. Glial cells have major roles in every stage of disease, from the earliest subtle variations in neural function, to the development of epi‐retinal membranes and tractional detachment. Therefore, having a firm understanding of the function of retinal glia is important in our understanding of retinal disease and is crucial for the development of new treatment strategies.

Blocking IL-17A Alleviates Diabetic Retinopathy in Rodents

“…Although IL-17RA is also expressed by other retinal cells, such as retinal astrocytes and RPE, in vitro investigation shows a weak inflammatory effect of RPE cells in response to IL-17A [55]. Accordingly, we propose that retinal Müller cells are a predominant target for IL-17A in DR. Müller cell abnormality has been linked to BRB breakdown and retinal neuronal dysfunction and death [56]. This supports our hypothesis that by inflammatory injury to retinal Müller cells, IL-17A accelerates DR progression.…”

“…Within the past decade, anti-VEGF agents have revolutionized the treatment of several retinal diseases, including diabetic macular edema (DME), for which anti-VEGF agents are now accepted as first-line treatment [56]. In contrast, the effects of anti-VEGF agents on the severity of DR aside from DME are more incompletely established [56].…”

In vitro effect of adenosine on the mRNA expression of Kir 2.1 and Kir 4.1 channels in rat retinal Müller cells at elevated hydrostatic pressure

“…Müller cells are responsible for the maintenance of homeostasis in the extracellular medium of the retina and protection of the neurons through the release of neurotrophins (19)(20)(21)(22). Moreover, Müller cells can also have altered expression and functioning potassium channels, with consequential alteration in ion homeostasis and development of edema in the retina.…”

Beta-2-Adrenergic Receptor Regulates Insulin Signaling to Reduce Cell Death in Müller Cells

“…59 Since Müller cells become activated and express increased glial fibrillary acidic protein levels in diabetes, 59 this suggests that the cells are nonhomeostatic, which will alter their regulation of inflammatory markers, glucose transport, oxidative stress, growth factors, and finally cell survival. 98,99 Previous studies from our lab have shown that Müller cells display increased inflammatory markers (specifically TNFreduced following -adrenergic receptor stimulation. 29 TNF-has been shown to play a major role in the induction of apoptosis in retinal cells, specifically during the onset of diabetic retinopathy.…”

“…131 Müller cells play an important role in the retina by providing nutrients to blood vessels, regulating ion concentrations, and initiating protection methods in times of stress. 58,59,98,127,131,132 One of the earliest disruptions in diabetic retinopathy is the activation of retinal Müller cells leading to an increase in GFAP, indicative of a stress in the retinal environment. 29,53,59,62,99,127,131,133,134 Müller cells have previously been shown to be protective to the eye in a normal setting, but with the onset of diabetic retinopathy, these cells exhibit deleterious effects such as increases in inflammatory cytokines, growth factors, and other toxic effects.…”