title: Ultrastructural abnormalities of the trabecular meshwork extracellular matrix in Cyp1b1-deficient mice.
abstract: Cytochrome P450 1B1 (CYP1B1) is highly expressed in human and murine ocular tissues during development. Mutations in this gene are implicated in the development of primary congenital glaucoma (PCG) in humans. Mice deficient in Cyp1b1 (Cyp1b1(-/-) ) present developmental abnormalities similar to human primary congenital glaucoma. The present work describes the ultrastructural morphology of the iridocorneal angle of 21 eyes from 1-week-old to 8-month-old Cyp1b1(-/-) mice. Morphometric and semiquantitative analysis of the data revealed that 3-week-old Cyp1b1(-/-) mice present a significantly (P < .005) decreased amount of trabecular meshwork (TM) collagen and higher TM endothelial cell and collagen lesion scores (P < .005) than age-matched controls. Collagen loss and lesion scores were progressively increased in older animals, with 8-month-old animals presenting severe atrophy of the TM. Our findings advance the understanding of the effects of CYP1B1 mutations in TM development and primary congenital glaucoma, as well as suggest a link between TM morphologic alterations and increased intraocular pressure.
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, Madison, WI, USA McPherson Eye Research Institute, University of Wisconsin, Madison, WI, USA lteixeira@wisc.edu.
authors.forename: L B C
authors.initials: LB
authors.lastname: Teixeira
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, Madison, WI, USA McPherson Eye Research Institute, University of Wisconsin, Madison, WI, USA.
authors.forename: R R
authors.initials: RR
authors.lastname: Dubielzig
authors.affiliation: McPherson Eye Research Institute, University of Wisconsin, Madison, WI, USA Department of Pediatrics, University of Wisconsin, Madison, WI, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Sorenson
authors.affiliation: McPherson Eye Research Institute, University of Wisconsin, Madison, WI, USA Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI, USA.
authors.forename: N
authors.initials: N
authors.lastname: Sheibani
mesh_terms: D000818:Animals; D065633:Cytochrome P-450 CYP1B1 / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005901:Glaucoma / Q000151:congenital* / Q000473:pathology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D018384:Oxidative Stress; D014129:Trabecular Meshwork / Q000648:ultrastructure*
chemical_list: C585498:Cyp1b1 protein, mouse; D065633:Cytochrome P-450 CYP1B1
keywords: CYP1B1; collagen fibrils; congenital glaucoma; electron microscopy; eye; mouse; oxidative stress; trabecular meshwork