Neuronal versus glial cell swelling in the ischaemic retina.
Under normal conditions, the pigment epithelium dehydrates the outer retina while Müller glial cells mediate the rapid water transport within the inner retina. Gliotic alterations of Müller cells may be implicated in the development of oedema in the post-ischaemic retina. Here, we suggest a mechanism of Müller 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 Ca(2+) 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 Müller 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 Müller 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 Müller cells may become a novel way to resolve both cytotoxic and vasogenic oedema in the retina.
Bringmann
Andreas
A
Department of Ophthalmology and Eye Clinic, Medical Faculty, University of Leipzig, Leipzig, Germany. bria@medizin.uni-leipzig.de
Uckermann
Ortrud
O
Pannicke
Thomas
T
Iandiev
Ianors
I
Reichenbach
Andreas
A
Wiedemann
Peter
P
D000818:Animals; D017209:Apoptosis; D051401:Aquaporin 4 / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D002199:Capillary Permeability; D048429:Cell Size; D006706:Homeostasis; D006801:Humans; D007511:Ischemia / Q000378:metabolism* / Q000473:pathology; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010211:Papilledema / Q000378:metabolism* / Q000473:pathology; D011188:Potassium / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism; D012171:Retinal Vessels / Q000378:metabolism* / Q000473:pathology; D014867:Water / Q000378:metabolism
D051401:Aquaporin 4; D015220:Calcium Channels; D017470:Receptors, Glutamate; D014867:Water; D011188:Potassium; D002118:Calcium