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S. M. Conley, D. M. Sherry, K. L. Arbogast, B. A. Nagel, J. R. Shackelford, S. J. Fliesler, M. I. Naash; Aquaporin 0 Is Crucial for Proper Synapse Formation Between Cones and on Cone Bipolar Cells. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5860.
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We have reported that Aquaporin 0 (AQP0), a plasma membrane protein involved in water homeostasis and previously thought to be lens-specific, is also expressed in retinal bipolar cells. Also, mice deficient in functional AQP0 have no cone-driven ERG b-wave. In this study, we evaluated the structural and electrophysiological consequences of expressing a non-functional form of AQP0 in the retina.
Retinal function in CatFr (which harbor a mutation in AQP0 that renders it non-functional) and in age-matched wild-type C57/Bl6 control mice was assessed by electroretinography (ERGs), while AQP0 expression and the integrity of retinal cells and synaptic circuits were assessed immunohistochemically (at 1-3 months of age). Electron microscopy was used to characterize ultrastructural features and to identify cytological defects.
AQP0 is expressed by rod and ON cone bipolar cells. In the absence of functional AQP0, ribbon synapses between cones and their ON bipolar cells are selectively disrupted. In contrast, ribbon synapses between rods and rod bipolar cells and flat contacts between cones and OFF cone bipolar cells appear essentially normal. Ultrastructurally, the outer plexiform layer in CatFr mice is disorganized with aberrant accumulation of membranous material in the dendritic processes. However, the absence of functional AQP0 does not alter the organization of bipolar cell terminals in the inner plexiform layer, nor apparently does it disrupt other retinal cell types or circuits.
Functional AQP0 appears to play an important and selective role in the establishment of synapses between cones and ON cone bipolar cells. This observation is novel: a role for AQP0 in synapse formation has not been described heretofore in any part of the nervous system, and is consistent with the observed functional phenotype.
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