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J. Kuchtey, M. Curtis, K. Gelatt, M. Kallberg, T. Rinkoski, A. Komaromy, R. Kuchtey; Invetigation of Cornea-Derived Transcript 6 (CDT6) as a Potential Glaucoma Protein. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3951.
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To investigate the role of cornea-derived transcript 6 (CDT6) protein in the pathogenesis of glaucoma.
Primary human trabecular meshwork (TM) cells were stimulated with dexamethasone and transforming growth factor beta (TGFb), and CDT6 protein levels in supernatants were determined by Western blotting. Localization of CDT6 protein in human anterior segment tissue was determined by immunohistochemistry. The levels of CDT6 protein in aqueous humor (AH) from glaucoma patients were compared with that obtained from non-glaucoma patients undergoing cataract surgery. The beagle model of primary open-angle glaucoma (POAG) was used to monitor CDT6 protein levels in canine AH with disease progression.
In human anterior segment tissue, CDT6 protein expression was highest in the deep stromal layer of cornea, near Schlemm's canal in the limbus, while the TM expressed little or no CDT6. Its differential express in the cornea and TM was confirmed by Western blotting. Secretion of CDT6 protein was induced by treatment of primary TM cells with dexamethasone, TGFb -1 and TGFb -2. More CDT6 protein was found in AH of glaucoma patients, as compared to controls. In individual POAG beagle dogs, the levels of CDT6 protein in the AH obtained every 6 months increased as severity of POAG progressed.
CDT6 is a secreted protein primarily produced by corneal cells and released into AH. The possibility that CDT6 protein is involved in glaucoma pathogenesis is supported by the fact that it is induced by dexamethasone and TGFb. Increased levels of CDT6 protein in AH of glaucoma patients is consistent with a pathogenic role. The increase in CDT6 protein in AH of POAG beagles, which are not treated with glaucoma medications, is also consistent with a pathogenic role of CDT6 protein in the development of glaucoma. The effect of CDT6 on the AH outflow facility through excessive deposition of extracellular matrix, and the mechanism of CDT6 induction by dexamethasone are currently being investigated.
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