Abstract
Purpose: :
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that plays a key role in controlling the expression of antioxidant and detoxification genes. Induction of Nrf2 protects the retina and retinal pigment epithelium (RPE) against photooxidative injury. The purpose of the study was to determine whether Nrf2 knockout mice develop accelerated degenerative changes in the retina over time, and to measure Nrf2 expression in response to laser-induced choroidal neovascularization (LCNV).
Methods: :
The retina and RPE of wild type and Nrf2 knockout mice were examined by light and electron microscopy. Laser photocoagulation was performed on wild type and Nrf2 null mice. At ten days, LCNV lesions were assessed by fluorescein angiography (FA). The mRNA levels of genes involved in oxidative stress, inflammation, and angiogenesis were measured by real-time RT-PCR and Western blot analyses.
Results: :
Differential expression of genes involved in antioxidant response and inflammation were detected between control and knockout mice. At 6 months, Nrf2 null mice showed apparently normal retina; however, their responses to laser intervention were more severe than the wild type mice. Higher VEGF mRNA expression in the retina of Nrf2 null mice was observed 5 to 7 days after laser laser photocoagulation compared to wild type mice.
Conclusions: :
Nrf2 gene knockout is associated with increased retinal vulnerability of the retina and RPE to environmental stress. The Nrf2-mediated antioxidant and detoxification pathways may play a key role in the pathological conditions associated with retinal degeneration.
Keywords: age-related macular degeneration • vascular endothelial growth factor • choroid: neovascularization