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• W2133321570 abstract "Heterozygous mutations in PAX6 are causative for aniridia, a condition that is frequently associated with juvenile glaucoma. Defects in morphogenesis of the iridocorneal angle, such as lack of trabecular meshwork differentiation, absence of Schlemm's canal and blockage of the angle by iris tissue, have been described as likely causes for glaucoma, and comparable defects have been observed in heterozygous Pax6-deficient mice. Here, we employed Cre/loxP-mediated inactivation of a single Pax6 allele in either the lens/cornea or the distal optic cup to dissect in which tissues both alleles of Pax6 need to be expressed to control the development of the tissues in the iridocorneal angle. Somatic inactivation of one allele of Pax6 exclusively from epithelial cells of lens and cornea resulted in the disruption of trabecular meshwork and Schlemm's canal development as well as in an adhesion between iris periphery and cornea in juvenile eyes, which resulted in the complete closure of the iridocorneal angle in the adult eye. Structural changes in the iridocorneal angle presumably caused a continuous increase in intraocular pressure leading to degenerative changes in optic nerve axons and to glaucoma. In contrast, the inactivation of a single Pax6 allele in the distal optic cup did not cause obvious changes in iridocorneal angle formation. We conclude that the defects in iridocorneal angle formation are caused by non-autonomous mechanisms due to Pax6 haploinsufficiency in lens or corneal epithelial cells. Pax6 probably controls the expression of signaling molecules in lens cells that regulate the morphogenetic processes during iridocorneal angle formation." @default.
• W2133321570 created "2016-06-24" @default.
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• W2133321570 date "2010-06-10" @default.
• W2133321570 modified "2023-10-18" @default.
• W2133321570 title "Reduced expression of Pax6 in lens and cornea of mutant mice leads to failure of chamber angle development and juvenile glaucoma" @default.
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• W2133321570 doi "https://doi.org/10.1093/hmg/ddq237" @default.
• W2133321570 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20538882" @default.
• W2133321570 hasPublicationYear "2010" @default.
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