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Enhanced retinal degeneration induced by sodium iodate in alphaB‐crystallin knockout mice
Author(s) -
Hinton David R,
Zhou Peng,
Kannan Ram
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.38.2
Subject(s) - retinal degeneration , chemistry , retinal , retina , protein kinase b , microbiology and biotechnology , apoptosis , endocrinology , medicine , biology , neuroscience , biochemistry
The aim of this study was to determine the effect of αB‐crystallin knockout on sodium iodate (NaIO3)‐induced retinal degeneration in mice. Time and dose dependent effects of intravenous NaIO3 (20–70 mg/kg for 3–21 days) on visual function, retinal pigment epithelium (RPE) and retinal neuronal loss, and signaling pathways involved were investigated. NaIO3 caused a time‐dependent decrease in a and b waves in the electroretinogram and progressive retinal degeneration. Absence of αB‐crystallin accelerated and augmented the retinal degeneration in NaIO3‐treated mice and was associated with increased retinal cell apoptosis. In vitro studies revealed increased accumulation of reactive oxygen species (ROS) in cultured human RPE cells after NaIO3 treatment, and ROS were significantly increased in RPE after αB‐crystallin siRNA knock down. Increased RPE apoptosis was found in low dose NaIO3‐treated RPE after αB‐crystallin siRNA knock down; however, necrosis was minimal. Upregulation of AKT phosphorylation and peroxisome proliferator‐activated receptor‐γ (PPARγ) was found in NaIO3‐treated human RPE which was suppressed in αB‐crystallin siRNA knock down RPE cells. Our data suggest that αB‐crystallin plays a critical role in protection of NaIO3 induced oxidative stress and retinal degeneration in part through upregulation of AKT phosphorylation and PPARγ expression.