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Francine F Behar-Cohen, Alexandre Moulin, Laurent Jonet, Emmanuelle Gelize, Alexandre Sellam, Patricia Crisanti; Aquaporin 4 and glymphatic drainage in the human macula. Invest. Ophthalmol. Vis. Sci. 2018;59(9):388. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Aquaporin 4 is a water chanel expressed in astrocytes and in retinal glial Müller cells (RMG) that facilitates water transport across plasma membranes in response to osmotic gradients, contributing to intra- and extracellular hydro-ionic regulation. In the rodent retina, AQP4 localized in RMG endfeet and around vessels, is down-regulated in most of retinal disease models, contributing to barrier alteration and gliosis. In the macula, the exact distribution of AQP4 and the consequences of disease state in AQP4 expression remains poorly unedrstood.The aim of this study is to analyze AQP4 distribution in the normal and diabetic macula.
Maculae from post mortem donors, and from enucleations have been processed for cryo-sections and for flat-mounts. Both diabetic, wet Age-Related Macular Degeneration and normal macula were studied. Immunohistochemistry for AQP4, RMG markers (glutamine synthetase, vimentin, GFAP, CRALBP), astrocyte markers (GFAP), and basal membrane (collagen IV) were used. Confocal microscopy was used to analyze flat-mounted retina and cryosections.
AQP4 is highly concentrated in the macula and more specifically in the fovea. In the avascular zone, AQP4 is expressed in GFAP positive cells at the roof of the fovea and all along RMG cone cells and along Z-shaped RMG cells. RMG cells follow the nerve fibers towards the optic nerve head, were AQP4 is expressed not only in astrocytes but also in RMG cells. AQP4 distribution at the glial cell membranes forms channel-like structures. The distribution and expression of AQP4 is altered by diabetes and AMD. RMG poorly express GFAP in diseases conditions.
AQP4 allows water extrusion from RMG cells but does not permit water entry through the water-impermeable retinal blood vessels. Thus, like in the brain, AQP4 function creates an hydraulic pathway along vessels, were fluid and proteins can migrate. The intense expression of AQP4 along RMG cells in the central avascular region of the macula suggests that a “gymphatic drainage” could also exist in the retina. Our study suggest that water and proteins could be eliminate from the fovea, towards the Z-shaped RMGs and then could follow RMG along nerve fibers to the optic nerve head. In pathologic states, the glymphatic system is disorganized explaining the specific location of fluid accumulation
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
Schematic representation of the glymphatic pathway created by AQP4 water drainage in the retina
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