title: Disruption of the blood-aqueous barrier and lens abnormalities in mice lacking lysyl oxidase-like 1 (LOXL1).
abstract: OBJECTIVE
  Exfoliation syndrome (ES) is commonly associated with glaucoma, premature cataracts, and other ocular and systemic pathologies. LOXL1 gene variants are significantly associated with ES; however, the role of the protein in ES development remains unclear. The purpose of this study was to characterize the ocular phenotype in Loxl1(-/-) (null) mice.
  
  
  METHODS
  Loxl1 null mice and strain-matched controls (C57BL) were evaluated by clinical and histologic analyses.
  
  
  RESULTS
  Anterior segment histology showed a pronounced vesiculation of the anterior lens in the null mice. The lesions were subcapsular and in direct apposition with the posterior iris surface. Fluorescein angiography showed increased diffusion of fluorescein into the anterior chamber of the null mice compared with age-matched controls (P = 0.003, two-tailed, unequal variance t-test), suggesting compromise of the blood-aqueous barrier. Intraocular pressure measurements were within the normal range (16.5 ± 2.0 mm Hg) in null mice up to 1 year of age. Immunohistochemistry showed decreased elastin in the iris and ciliary body in the null mouse compared with controls.
  
  
  CONCLUSIONS
  Elimination of LOXL1 in mice impairs the blood-aqueous humor barrier in the ocular anterior segment and causes lens abnormalities consistent with cataract formation, but does not result in deposition of macromolecular material or glaucoma. These results show that mice lacking LOXL1 have some ES features but that complete disease manifestation requires other factors that could be genetic and/or environmental.
authors.affiliation: Department of Ophthalmology, Harvard Medical School, Howe, Berman Gund and Angiogenesis Laboratories, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts.
authors.forename: Janey L
authors.initials: JL
authors.lastname: Wiggs
authors.forename: Basil
authors.initials: B
authors.lastname: Pawlyk
authors.forename: Edward
authors.initials: E
authors.lastname: Connolly
authors.forename: Michael
authors.initials: M
authors.lastname: Adamian
authors.forename: Joan W
authors.initials: JW
authors.lastname: Miller
authors.forename: Louis R
authors.initials: LR
authors.lastname: Pasquale
authors.forename: Ramez I
authors.initials: RI
authors.lastname: Haddadin
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Grosskreutz
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Rhee
authors.forename: Tiansen
authors.initials: T
authors.lastname: Li
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000235:genetics*; D000818:Animals; D000867:Anterior Chamber / Q000378:metabolism; D018916:Blood-Aqueous Barrier / Q000201:enzymology / Q000473:pathology*; D002386:Cataract / Q000201:enzymology / Q000473:pathology*; D002924:Ciliary Body / Q000378:metabolism; D004549:Elastin / Q000378:metabolism; D017889:Exfoliation Syndrome / Q000201:enzymology / Q000473:pathology*; D019793:Fluorescein / Q000378:metabolism; D005451:Fluorescein Angiography; D019084:Fluorescent Antibody Technique, Indirect; D005456:Fluorescent Dyes / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D015151:Immunoblotting; D007429:Intraocular Pressure; D007498:Iris / Q000378:metabolism; D007908:Lens, Crystalline / Q000201:enzymology / Q000648:ultrastructure*; D051379:Mice; D008810:Mice, Inbred C57BL; D016253:Microscopy, Immunoelectron; D010641:Phenotype; D016133:Polymerase Chain Reaction
chemical_list: D005456:Fluorescent Dyes; D004549:Elastin; D000594:Amino Acid Oxidoreductases; C482019:Loxl1 protein, mouse; D019793:Fluorescein
keywords: LOXL1; exfoliation syndrome; glaucoma