AQUAPORIN-4 WATER CHANNEL PROTEIN IN THE RAT RETINA AND OPTIC-NERVE -POLARIZED EXPRESSION IN MULLER CELLS AND FIBROUS ASTROCYTES

The water permeability of cell membranes differs by orders of magnitud e, and most of this variability reflects the differential expression o f aquaporin water channels. Mle have recently found that the CNS conta ins a member of the aquaporin family, aquaporin-4 (AQP4). As a prerequ isite for understanding the cellular handling of water during neuronal activity we have investigated the cellular and subcellular expression of AQP4 in the retina and optic nerve where activity-dependent ion fl uxes have been studied in detail. In situ hybridization with digoxigen in-labeled riboprobes and immunogold labeling by a sensitive postembed ding procedure demonstrated that AQP4 and AQP4 mRNA were restricted to glial cells, including Muller cells in the retina and fibrous astrocy tes in the optic nerve. A quantitative immunogold analysis of the Mull er cells showed that these cells exhibited three distinct membrane com partments with regard to AQP4 expression. End feet membranes (facing t he vitreous body or blood vessels) were 10-15 times more intensely lab eled than non-end feet membranes, whereas microvilli were devoid of AQ P4. These data suggest that Muller cells play a prominent role in the water handling in the retina and that they direct osmotically driven w ater flux to the vitreous body and vessels rather than to the subretin al space. Fibrous astrocytes in the optic nerve similarly displayed a differential compartmentation of AQP4. The highest expression of AQP4 occurred in end feet membranes, whereas the membrane domain facing the nodal axolemma was associated with a lower level of immunoreactivity than the rest of the membrane. This arrangement may allow transcellula r water redistribution to occur without inducing inappropriate volume changes in the perinodal extracellular space.