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• W2896575748 endingPage "18.2018" @default.
• W2896575748 startingPage "ENEURO.0260" @default.
• W2896575748 abstract "<h3>Abstract</h3> Glaucoma is a leading cause of irreversible vision loss due to retinal ganglion cell (RGC) degeneration that develops slowly with age. Elevated intraocular pressure (IOP) is a significant risk factor, although many patients develop glaucoma with IOP in the normal range. Mutations in microfibril-associated genes cause glaucoma in animal models, suggesting the hypothesis that microfibril defects contribute to glaucoma. To test this hypothesis, we investigated IOP and functional/structural correlates of RGC degeneration in mice of either sex with abnormal microfibrils due to heterozygous <i>Tsk</i> mutation of the fibrilin-1 gene (<i>Fbn1^Tsk</i>^/+). Although IOP was not affected, <i>Fbn1^Tsk</i>^/+ mice developed functional deficits at advanced age consistent with glaucoma, including reduced RGC responses in electroretinogram (ERG) experiments. While RGC density in the retina was not affected, the density of RGC axons in the optic nerve was significantly reduced in <i>Fbn1^Tsk</i>^/+ mice. However, reduced axon density correlated with expanded optic nerves, resulting in similar numbers of axons in <i>Fbn1^Tsk</i>^/+ and control nerves. Axons in the optic nerves of <i>Fbn1^Tsk</i>^/+ mice were significantly enlarged and axon diameter was strongly correlated with optic nerve area, as has been reported in early pathogenesis of the DBA/2J mouse model of glaucoma. Our results suggest that microfibril abnormalities can lead to phenotypes found in early-stage glaucomatous neurodegeneration. Thinning of the elastic fiber-rich pia mater was found in <i>Fbn1^Tsk</i>^/+ mice, suggesting mechanisms allowing for optic nerve expansion and a possible biomechanical contribution to determination of axon caliber." @default.
• W2896575748 created "2018-10-26" @default.
• W2896575748 creator A5004283621 @default.
• W2896575748 creator A5030701924 @default.
• W2896575748 creator A5033766833 @default.
• W2896575748 creator A5063990859 @default.
• W2896575748 date "2018-09-01" @default.
• W2896575748 modified "2023-10-14" @default.
• W2896575748 title "Enlarged Optic Nerve Axons and Reduced Visual Function in Mice with Defective Microfibrils" @default.
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