Differences in Müller's glia between the central and peripheral retina and its effect in glaucoma

Abstract

Glaucoma is a neurodegenerative disease and the leading cause of irreversible blindness in the world, whose main risk factor is increased intraocular pressure. When visual problems are first detected in patients with glaucoma, already half of the retinal ganglion cells (RGCs), the neurons that send visual information from the eye to the brain, have died principally in the peripheral retina. The timeframe of cell death is prolonged, lasting even decades after an initial diagnosis. Müller glia (MG) are the main macroglial cell in the retina, play prominent roles regulating normal and pathological physiology and react to neuronal injury in glaucoma. The change to a reactive phenotype of MG initiates signalling cascades that may serve a neuroprotective role, but may also proceed to promote damaging effects on RGCs. However, the underlying mechanisms and signalling pathways that specifically promote protective versus destructive roles of reactive glial cells are mostly unclear.Using cell cultures of Müller cells, retinal ganglion cells or cocultures subjected to hydrostatic pressure, we have been able to prove that Müller cells in the periphery react to pressure by secreting harmful proteins that induce ganglion cell death. Proteomic analysis has provided us with information on the different behaviour of Müller cells in the periphery versus those in the center.Elevated hydrostatic pressure on MG induces the expression of proteins associated to apoptosis, oxidative stress and inflammation in the peripheral MG. This study confirms that MG could have a role in RGCs death in glaucoma opening new avenues for research. Preventing MG response to elevated pressure, MG can neuroprotect RGCs in early stages of glaucoma.Supported by ELKARTEK (KK‐2019/00086), MINECO‐Retos (PID2019‐111139RB‐I00), PIBA (2020_1_0026), Grupos Consolidados Gobierno Vasco, UPV/EHU: