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Ling Zhu, Yuyi You, Ting Zhang, Mark C Gillies; The differential expression of aquaporin-4 (AQP4) in Müller cells from human macular and peripheral retina.. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4392.
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© ARVO (1962-2015); The Authors (2016-present)
Why the macula is more vulnerable to developing disease than the rest of the is poorly understood. A key difference between the macula and the peripheral retina may be the nature of its Müller cells. Dysfunction of AQP4, a water channel in Müller cells, may be associated with age related macular degeneration (AMD) and diabetic retinopathy (DR). The purpose of this study was to evaluate the differential expression of AQP4 in Müller cells from macular and peripheral retina to understand better its role in the pathogenesis of macular disease.
We first assessed the topographic distribution of AQP4 expression using a series of fresh 2 mm retinal punches from different locations across the retinas of 4 human donors by western blot. We then performed immunofluorescent staining on frozen cross sections of the human macula and peripheral retinas using CRALBP (a Müller cell marker) and AQP4 antibodies. Whole mount immunofluorescent staining was performed to explore the distribution pattern of AQP4 across the different regions of the retina.
We found by Western blotting that the macula expressed significantly higher levels of AQP4 than the mid-peripheral (5-7 mm from the fovea) and far-peripheral (9-11 mm from fovea) areas of the retina. We did not find significant differences in AQP4 expression in superior, inferior, nasal or temporal-peripheral retinal areas. Immunofluorescent staining of AQP4 in the human retina was predominantly observed in Müller cells, evidenced by strong co-localisation with CRALBP. We also found that AQP4 was mainly expressed in the Henle fibre layer and the outer limiting membrane in the centre of the macula.
The differential expression of AQP4 in the central and peripheral retina may be related to specific roles of Müller cells in these different regions. The fact that macular Müller cells express significantly higher levels of AQP4 may provide insights into the pathogenesis and treatment of AMD and DR, which tend to involve the macula preferentially.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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