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M. Ogata, M. Inatani, K. Iwao, H. Tanihara; Heparan Sulfate Is Required for the Development of Optic Nerve Head. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1229.
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Heparan sulfate (HS) and HS proteoglycan are known to bind to numerous proteins such as adhesion molecules and chemoattractants for optic nerve guidance. In the present study, we investigated whether the morphogenesis of optic nerve head depends on HS.
We conditionally disrupted a HS-polymerizing enzyme, EXT1, in the mice embryo using Cre-loxP system when axons of retinal ganglion cells started to extend toward the optic disk. Mice carrying transgenic gene for tamoxifen-induced Cre enzyme were bred to mice with loxP-modified EXT1 allele. To disrupt EXT1 gene during optic nerve head formation, tamoxifen was injected to the embryos carrying EXT1-floxed allele and Cre gene.
Compared with wild-type embryos, HS-deficient embryos displayed remarkable misguidance of ganglion cell axons in the retina. The disturbed morphogenesis of the optic nerve head was closely similar to the phenotype in mice lacking netrin-1, which is a HS-binding guidance molecule.
HS deficiency leads to abnormal optic nerve head morphogenesis. The finding suggests that HS may regulate the function of guidance molecules in the optic disk.
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