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Sotaro Mori, Takuji Kurimoto, Akiko Miki, Sentaro Kusuhara, Makoto Nakamura; Deletion of Aqp9 in mice enhances retinal ganglion cell death after optic nerve injury. Invest. Ophthalmol. Vis. Sci. 2019;60(9):655.
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© ARVO (1962-2015); The Authors (2016-present)
Aquaporins are the family of membrane channel proteins that transport water, glycerol, lactate, etc. across cellular membranes. Recently, we have revealed that aquaporin9 (AQP9) expresses in the retinal ganglion cells (RGC) and astrocytes and confers protective effects on retinal neuronal degeneration via lactate transporter in vitro (Akashi et al. 2015). On the other hand, it has shown that AQP9 co-localizes and interacts with monocarboxylate transporters (MCTs), a type of lactate transporters in hippocampus neurons (Tescarollo F et al. 2014). Thus, in this study, we investigated whether AQP9 is responsible for RGC survival in conjunction with MCTs in vivo.
Under anesthesia, an optic nerve of wild type (WT) and Aqp9 knockout (Aqp9KO) mice were crushed by forceps (optic nerve crush, ONC). The retinas were removed for immunohistochemistry and Western blot analysis before and 7 days after ONC. To evaluate RGC survival, the number of Tuj1-immunolabeled cells at the eight pre-specified flat-mounted retinal areas was counted and averaged. To identify the interaction between AQP9 and MCTs (MCT1 ,2, and 4), Western blot analysis with anti-MCTs antibodies of immunoprecipitated samples with anti-Aqp9 antibody was performed.
In the untreated retinas, there was no significant difference in Tuj1-positive cell density between WT mice (2908±348/mm2, n=8) and Aqp9KO mice (2803±487/mm2, n=8) (unpaired t-test, p=0.64). However, 7 days after ONC, Tuj1-positive cell density was significantly lower in Aqp9KO mice (1179 ± 224/mm2, n=8) than in WT mice (1627 ± 94/mm2, n=8) (unpaired t-test: p<0.01). Western blot analyses revealed the co-expression of AQP9 and all types of MCTs. However the co-expression of MCT1 and MCT4 with AQP9 decreased after ONC compared with that before ONC.
Aqp9 deletion significantly enhances RGC death after ONC, suggesting that AQP9 acts as a protective player in injured RGCs probably via lactate transport as an energy substrate, given the co-expression of AQP9 with MCTs in the retina.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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