A role for aquaporin-4 in fluid regulation in the inner retina

Many diverse retinal disorders are characterized by retinal edema; yet, little experimental attention has been given to understanding the fundamental mechanisms underlying and contributing to these fluid-based disorders. Water transport in and out of cells is achieved by specialized membrane channels, with most rapid water transport regulated by transmembrane water channels known as aquaporins (AQPs). The predominant AQP in the mammalian retina is AQP4. which is expressed on the Muller glial cells. Muller cells have previously been shown to modulate neuronal activity by modifying the concentrations of ions, neurotransmitters, and other neuroactive Substances within the extracellular space between the inner and the outer limiting membrane. In doing so, Muller cells maintain extracellular homeostasis, especially with regard to the spatial buffering of extracellular potassium (K+) via inward rectifying K+ channels (Kir channels). Recent Studies of water transport and the spatial buffering of K+ through glial cells have highlighted the involvement of both AQP4 and Kir channels in regulating the extracellular environment in the brain and retina. As both glial functions are associated with neuronal activation, controversy exists in the literature as to whether the relationship is functionally dependent. It is argued in this review that as AQP4 channels are likely to be the conduit for facilitating fluid homeostasis in the inner retina during light activation, AQP4 channels are also likely to play a consequent role in the regulation of ocular volume and growth. Recent research has already shown that the level of AQP4 expression is associated with environmentally driven manipulations of light activity on the retina and the development of myopia.