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• W3048201543 startingPage "101681" @default.
• W3048201543 abstract "Sorsby Fundus Dystrophy (SFD) is a rare inherited autosomal dominant macular degeneration caused by specific mutations in TIMP3. Patients with SFD present with pathophysiology similar to the more common Age-related Macular Degeneration (AMD) and loss of vision due to both choroidal neovascularization and geographic atrophy. Previously, it has been shown that RPE degeneration in AMD is due in part to oxidative stress. We hypothesized that similar mechanisms may be at play in SFD. The objective of this study was to evaluate whether mice carrying the S179C-Timp3 mutation, a variant commonly observed in SFD, showed increased sensitivity to oxidative stress. Antioxidant genes are increased at baseline in the RPE in SFD mouse models, but not in the retina. This suggests the presence of a pro-oxidant environment in the RPE in the presence of Timp3 mutations. To determine if the RPE of Timp3 mutant mice is more susceptible to degeneration when exposed to low levels of oxidative stress, mice were injected with low doses of sodium iodate. The RPE and photoreceptors in Timp3 mutant mice degenerated at low doses of sodium iodate, which had no effect in wildtype control mice. These studies suggest that TIMP3 mutations may result in a dysregulation of pro-oxidant—antioxidant homeostasis in the RPE, leading to RPE degeneration in SFD." @default.
• W3048201543 created "2020-08-13" @default.
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• W3048201543 date "2020-10-01" @default.
• W3048201543 modified "2023-10-01" @default.
• W3048201543 title "The retinal pigment epithelium in Sorsby Fundus Dystrophy shows increased sensitivity to oxidative stress-induced degeneration" @default.
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• W3048201543 doi "https://doi.org/10.1016/j.redox.2020.101681" @default.
• W3048201543 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7767753" @default.
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