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Published in: Japanese Journal of Ophthalmology 1/2013

01-01-2013 | Laboratory Investigation

Renin–angiotensin system involvement in the oxidative stress-induced neurodegeneration of cultured retinal ganglion cells

Authors: Yoko Ozawa, Kenya Yuki, Reiko Yamagishi, Kazuo Tsubota, Makoto Aihara

Published in: Japanese Journal of Ophthalmology | Issue 1/2013

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Abstract

Purpose

To analyze the influence of oxidative stress on retinal ganglion cells (RGCs) by using a selective culture system of rat RGCs.

Methods

Rat RGCs were purified by a two-step immunopanning procedure and cultured either with or without antioxidant (AO) compounds. Reactive oxygen species (ROS) in RGCs were analyzed using dihydroethidium. Expression of angiotensin II, cleaved caspase 3, and netrin-1 was analyzed by immunocytochemistry. Live RGCs were detected by use of calcein-acetoxymethyl ester. The roles of angiotensin II type 1 receptor (AT1R) signaling and netrin-1 were analyzed by use of an AT1R blocker (telmisartan) and an anti-netrin-1 neutralizing antibody, respectively.

Results

ROS and angiotensin II were induced in RGCs cultured without AO compounds (AO−). In these cultures, the number of live RGCs decreased and expression of cleaved and activated caspase 3 increased, but these changes were attenuated by addition of the AT1R blocker. Reduction in netrin-1 expression under the AO− condition was also prevented by the AT1R blocker. The AT1R blocker’s effects on RGC survival and reduction in cleaved caspase 3-positive cells were cancelled by the anti-netrin-1 neutralizing antibody.

Conclusions

Oxidative stress induced cell death through AT1R signaling and netrin-1 reduction in cultured RGCs.
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Metadata
Title
Renin–angiotensin system involvement in the oxidative stress-induced neurodegeneration of cultured retinal ganglion cells
Authors
Yoko Ozawa
Kenya Yuki
Reiko Yamagishi
Kazuo Tsubota
Makoto Aihara
Publication date
01-01-2013
Publisher
Springer Japan
Published in
Japanese Journal of Ophthalmology / Issue 1/2013
Print ISSN: 0021-5155
Electronic ISSN: 1613-2246
DOI
https://doi.org/10.1007/s10384-012-0204-x

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