Negative impact of AQP-4 channel inhibition on survival of retinal ganglion cells and glutamate metabolism after crushing optic nerve.

Experimental Eye Research
Yuko NishikawaTsunehiko Ikeda

Abstract

The purpose of this study was to determine whether inhibition of aquaporin 4 (AQP4) is neuroprotective or neurodestructive after crushing the optic nerve of rats. The left optic nerves of rats were crushed, and TGN-020 (5.0 mg/kg, crush TGN-020) or its vehicle (DMSO, crush placebo) was injected intraperitoneally just after the crushing. As controls, the left optic nerves were exposed but not touched in other rats (sham controls). The retinal damages were determined by the density of retinal ganglion cells (RGCs) and the ratio of BAX/Bcl-2 on day 7. The glutamate level in the optic nerve on day 1 after the crushing was determined. The expressions of glutamine synthetase, glutamate-aspartate transporter (GLAST), and AQP4 were determined on day 3 by immunoblotting. The effects of AQP4 inhibition on the glutamate-induced changes of AQP4 expression and on the glutamate uptake were determined for optic nerve astrocytes in culture. The results showed that the density of RGCs was 2040 ± 91.3 cells/mm(2) (n = 6) in the sham control, and it was significantly decreased to 1072 ± 134.3 cells/mm(2) after crushing the optic nerve (P < 0.0001, crush placebo, n = 7; Fisher). An intraperitoneal injection of TGN-020 led to a further significant ...Continue Reading

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Citations

Jul 22, 2016·International Journal of Molecular Sciences·Barbara AmannCornelia A Deeg
Feb 17, 2018·Neural Regeneration Research·Zheng-Ru HuangQing-Huai Liu
Jan 30, 2020·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·Souphatsone HouattongkhamNobuyuki Hamajima

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