Müller Glial Cells in Retinal Disease

Abstract

Virtually all pathogenic stimuli activate Müller cells. Reactive Müller cells exert protective and toxic effects on photoreceptors and neurons. They contribute to oxidative stress and glutamate toxicity due to malfunctions of glutamate uptake and glutathione synthesis. Downregulation of potassium conductance disrupts transcellular potassium and water transport, resulting in neuronal hyperexcitability and edema. Protective effects of reactive Müller cells include upregulation of adenosine 5′-triphosphate (ATP)-degrading ectoenzymes, which enhances the extracellular availability of the neuroprotectant adenosine, abrogation of the osmotic release of ATP, which might protect retinal ganglion cells from apoptosis, and the release of antioxidants and neurotrophic factors. The dedifferentiation of reactive Müller cells to progenitor-like cells might have an impact on future therapeutic approaches. A better understanding of the gliotic mechanisms will be helpful in developing efficient therapeutic strategies aiming at increased protective and regenerative properties and decreased toxicity of reactive Müller cells.

Pulmonary Surfactant Protein A Is Expressed in Mouse Retina by Muller Cells and Impacts Neovascularization in Oxygen-Induced Retinopathy

“…Glutamine synthetase has been shown to be a relatively specific marker of Müller cells in both the developing and mature retina. 49 Several studies have shown that differentiation of Müller cells and glial cell elements in the mouse retina begins quite early. Colocalization of SP-A was highly prominent with GS at P5.…”

Elevated cell proliferation and VEGF production by high-glucose conditions in Müller cells involve XIAP

“…[6][7][8] Reactive gliosis including hypertrophy, enlargement of soma, and proliferation are the most obvious pathological changes that occur in Mü ller cells during diabetes. 9,10 Moreover, increased VEGF expression in Mü ller cells under hyperglycemic conditions is one of the major contributors to pathological intraocular neovascularization.…”

Biomarkers in Diabetic Retinopathy

“…Retinal glial cells are involved in the interaction between vascular, neural, and retinal compartments. Müller cells that surround retinal blood vessels are assumed to modulate vascular permeabilty, blood flow, and vascular cell survival [139][140][141][142][143].…”