Neuronal versus glial cell swelling in the ischaemic retina

Under normal conditions, the pigment epithelium dehydrates the outer retina while Muller glial cells mediate the rapid water transport within the inner retina. Gliotic alterations of Muller cells may be implicated in the development of oedema in the post-ischaemic retina. Here, we suggest a mechanism of Muller cell-supported neuronal cell swelling and apoptosis in the ischaemic retina. During ischaemia, over-excitation of ionotropic glutamate receptors leads to neuronal cell depolarization that causes excess Ca2+ influx into the cells, and to activation of the apoptosis machinery. The ion fluxes into the retinal neurons are associated with water movements that are mediated by aquaporin-4 water channels expressed by Muller cells and result in neuronal cell swelling. After reperfusion, the glial cells may swell due to the down-regulation of their K+ conductance, which results in intracellular K+ overload and water movements from the blood and vitreous into the cells. An inhibition of the glial cell-mediated water movements during ischaemic episodes should reduce the ion shifts at the neuronal synapses, resulting in decreased neuronal cell swelling and apoptosis. An inhibition of the water movements in the post-ischaemic phase may prevent cytotoxic Muller cell swelling but may impair the fluid clearance from retinal tissue in the presence of vasogenic oedema. Thus, pharmacological modification of the ion and fluid clearance functions of Muller cells may become a novel way to resolve both cytotoxic and vasogenic oedema in the retina.