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G.J. McLellan, M.H. Kuehn, N.M. Ellinwood, C.Y. Kim, J. Jens, K.J. Sigle, C. Petersen; A Feline Model of Primary Congenital Glaucoma – Histopathological and Genetic Characterization . Invest. Ophthalmol. Vis. Sci. 2006;47(13):175.
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© ARVO (1962-2015); The Authors (2016-present)
To characterize histomorphological abnormalities of the aqueous outflow pathways, elucidate the mode of inheritance and evaluate candidate genes in a feline model of primary congenital glaucoma.
A viable breeding colony was established and an expanded, informative pedigree generated. Disease status was determined, by clinical evaluation (including tonometry, slit–lamp biomicroscopy and indirect ophthalmoscopy) and/or histopathological evaluation, in 37 affected Siamese cats and 34 F1 out–crossed cats. Dominant inheritance was assessed by Χ2 analyses of pairings between affected cats and both normal Siamese, and normal domestic short–haired cats. Blood or tissue samples were obtained for molecular genetic analyses from all cats. The genomic organization of the feline PITX2, MYOC and CYP1B1 genes was determined and select members of the pedigree were evaluated for potential disease causing sequence variations.
Histopathological findings in affected cats, when compared to normal cats, included arrested development of the uveal trabecular meshwork and the angular aqueous plexus (analogous to Schlemm’s canal) evident by 3 weeks of age, a paucity of intrascleral blood vessels, and hypoplasia of the iris and ciliary body stroma. Χ2 analyses yielded rejection of a simple dominant mode of inheritance (p<0.025) and rejection of dominant inheritance within a Siamese tyrosinase–mutant genetic background (p<0.1). Assessment of autosomal recessive inheritance is on–going, pending phenotypic characterization of back–crossed kittens. While allelic differences in the PITX2, MYOC and CYP1B1 genes were observed in individual animals, none of these appeared to be related to the disease phenotype.
In this feline model of inherited congenital glaucoma, arrest in early post–natal development of the aqueous outflow system is associated with moderate elevation in intraocular pressure and slowly progressive loss of vision. Breeding strategies have focused on generation of a highly informative pedigree, as well as production of affected animals. Our data suggest that mutations in a novel gene may be responsible for the development of glaucoma in these animals. Linkage analysis is currently underway to determine the chromosomal location of the underlying genetic defect.
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