期刊
REDOX BIOLOGY
卷 34, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.redox.2020.101469
关键词
Oxidative stress; Iron; Photoreceptor; Retinal pigment epithelium (RPE)
资金
- National Institutes of Health (NIH) [EY015240]
- Research to Prevent Blindness
- China Scholarship Council (CSC) [201706230076]
- Paul and Evanina Bell Mackall Foundation Trust
- FM Kirby Foundation
Iron has been implicated in the pathogenesis of retinal degenerative diseases, including ocular siderosis. However, the mechanisms of iron-induced retinal toxicity are incompletely understood. Previous work shows that intravitreal injection of Fe2+ leads to photoreceptor (PR) oxidative stress, resulting in PR death within 14 days, and cones are more susceptible than rods to iron-induced oxidative damage. In order to further investigate the mechanism of intravitreal iron-induced retinal toxicity and shed light on mechanisms of iron-induced re- tinopathy in other mouse models, Fe2+ , Fe3+ , or saline were injected into the vitreous of adult wild-type mice. Pre-treatment with Ferrostatin-1 was used to investigate whether iron-induced retinal toxicity resulted from ferroptosis. Color and autofluorescence in vivo retinal imaging and optical coherence tomography were per- formed on day 2 and day 7 post-injection. Eyes were collected for quantitative PCR and Western analysis on day 1 and for immunofluorescence on both day 2 and 7. In vivo imaging and immunofluorescence revealed that Fe2+ , but not Fe3+ , induced PR oxidative damage and autofluorescence on day 2, resulting in PR death and retinal pigment epithelial cell (RPE) autofluorescence on day 7. Quantitative PCR and Western analysis on day 1 in- dicated that both Fe2+ and Fe3+ induced iron accumulation in the retina. However, only Fe2+ elevated levels of oxidative stress markers and components of ferroptosis in the retina, and killed PRs. Ferrostatin-1 failed to protect the retina from Fe2+-induced oxidative damage. To investigate the mechanism of Fe2+-induced RPE autofluorescence, rd10 mutant mice aged 6 weeks, with almost total loss of PRs, were given intravitreal Fe2+ or Fe3+ injections: neither induced RPE autofluorescence. This result suggests Fe2+-induced RPE autofluorescence in wild-type mice resulted from phagocytosed, oxidized outer segments. Together these data suggest that in- traretinal Fe2+ causes PR oxidative stress, leading to PR death and RPE autofluorescence.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据