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Akiko Miki, Akiyasu Kanamori, Maiko Naka, Akira Negi, Makoto Nakamura; The Association Of Altered Aquaporin 9 Expression With Apoptosis Of Retinal Ganglion Cells. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5338.
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Aquaporins are a family of integral membrane proteins that allow water to cross the plasma membrane. They are critically involved in the maintenance of ionic and osmotic balance in the central nervous system (CNS). Aquaporin 9(AQP9) belongs to an aquaglyceroporin, is permeable to non-charged solutes such as lactate, an energy substrate in the CNS, and is reportedly expressed in retinal ganglion cells (RGCs). Previously we reported that elevated intraocular pressure reduced the AQP9 expression in rat RGCs. However, the causative relationship between the AQP9 loss and RGC death remains unknown. The purpose for this study is to investigate the association of altered AQP9 expression with apoptotic death of RGCs.
RGC5 cells were deprived of serum and the optic nerve was transected to induce apoptosis of RGCs in rats. The retinal and RGC5 AQP9 expression at various time points was quantified by real time RT-PCR and western blotting. Cell survival was assessed by Live/Dead assay. The effect of AQP9 knockdown using short interference RNA on the RGC5 apoptosis was evaluated by activated caspase-3 immunohistochemistry.
Both serum deprivation and optic nerve transection reduced protein expression of AQP9 (p= 0.0067 and p= 0.01,respectively).The AQP9 gene expression was also reduced in the latter (p=0.0012). The AQP9 knockdown accelerated the total number of death (p= 0.011) and apoptosis (p<0.001) of serum-deprived RGC5 cells.
AQP9 plays a critical role in RGC survival. The reduced expression of AQP9 induces apoptotic death of RGCs.
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