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Takashi Ueta, Tatsuya Inoue, Yasuhiro Tamaki, Hirotaka Imai, Yasuo Yanagi; Gpx4 As A Critical Anti-oxidant Enzyme For Photoreceptor Survival. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4422.
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© ARVO (1962-2015); The Authors (2016-present)
Oxidative stress has been believed to be an important pathogenic factor in retinal degeneration. However, the endogenous antioxidant system which is critical for the photoreceptor cell survival has remained unknown. Here we show glutathione peroxidase 4 (GPx4), an anti-oxidative enzyme involved in the cell-membrane bound phospholipid oxidation reduction, is a single anti-oxidant enzyme necessary for the photoreceptor cell survival, and lack of GPx4 in the mouse photoreceptor cells leads to a rapid retinal degeneration.
The photoreceptor-specific conditional knockout (CKO) mice of GPx4 were created by intersecting Crx-Cre transgenic mice and loxP/GPx4 mice. Retinal morphology was investigated by light microscopic analysis and the cellular differentiation into the rod and cone photoreceptor cells was evaluated by the immunofluorescent staining. The mechanism of the photoreceptor loss was tested by TUNEL.
In wild type mice GPx4 is expressed in every layer of the neural retina, especially prominent in the inner segment of the photoreceptor cells. The photoreceptors of the CKO mice showed the differentiation into the rod and cone cells at P12 as evidenced by positive immunostaing with rhodopsin antibody and PNA labeling, respectively. The microscopic analysis has shown that the following rod outer segments formation was impaired and subsequently massive cellular degeneration characterized by TUNEL positive cell death occurs. No photoreceptor cell was observed by P21.
GPx4 is a critical anti-oxidant enzyme for the photoreceptor survival.
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