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

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

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)126-132
Number of pages7
JournalJapanese Journal of Ophthalmology
Volume57
Issue number1
DOIs
Publication statusPublished - 2013 Jan

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Retinal Ganglion Cells
Renin-Angiotensin System
Cultured Cells
Oxidative Stress
Angiotensin II Type 1 Receptor Blockers
Antioxidants
Caspase 3
Angiotensin Type 1 Receptor
Neutralizing Antibodies
Angiotensin II
Reactive Oxygen Species
netrin-1
Cell Survival
Cell Death
Immunohistochemistry

Keywords

  • Angiotensin II
  • Netrin-1
  • Neuroprotection
  • Oxidative stress
  • Retina

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Renin-angiotensin system involvement in the oxidative stress-induced neurodegeneration of cultured retinal ganglion cells. / Ozawa, Yoko; Yuki, Kenya; Yamagishi, Reiko; Tsubota, Kazuo; Aihara, Makoto.

In: Japanese Journal of Ophthalmology, Vol. 57, No. 1, 01.2013, p. 126-132.

Research output: Contribution to journalArticle

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