Disruption of the blood-aqueous barrier and lens abnormalities in mice lacking Lysyl Oxidase-Like 1 (LOXL1)

Janey L. Wiggs, Basil Pawlyk, Edward Connolly, Michael Adamian, Joan W. Miller, Louis R. Pasquale, Ramez I. Haddadin, Cynthia L. Grosskreutz, Douglas J. Rhee, Tiansen Li

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Purpose. 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.

Original languageEnglish (US)
Pages (from-to)856-864
Number of pages9
JournalInvestigative Ophthalmology and Visual Science
Volume55
Issue number2
DOIs
StatePublished - Jan 14 2014

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Blood-Aqueous Barrier
Protein-Lysine 6-Oxidase
Lenses
Exfoliation Syndrome
Iris
Glaucoma
Cataract
Ciliary Body
Elastin
Aqueous Humor
Fluorescein Angiography
Anterior Chamber
Fluorescein
Intraocular Pressure
Histology
Reference Values
Immunohistochemistry
Pathology
Phenotype

Keywords

  • Exfoliation syndrome
  • Glaucoma
  • LOXL1

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Wiggs, Janey L. ; Pawlyk, Basil ; Connolly, Edward ; Adamian, Michael ; Miller, Joan W. ; Pasquale, Louis R. ; Haddadin, Ramez I. ; Grosskreutz, Cynthia L. ; Rhee, Douglas J. ; Li, Tiansen. / Disruption of the blood-aqueous barrier and lens abnormalities in mice lacking Lysyl Oxidase-Like 1 (LOXL1). In: Investigative Ophthalmology and Visual Science. 2014 ; Vol. 55, No. 2. pp. 856-864.
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abstract = "Purpose. 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.",
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Wiggs, JL, Pawlyk, B, Connolly, E, Adamian, M, Miller, JW, Pasquale, LR, Haddadin, RI, Grosskreutz, CL, Rhee, DJ & Li, T 2014, 'Disruption of the blood-aqueous barrier and lens abnormalities in mice lacking Lysyl Oxidase-Like 1 (LOXL1)', Investigative Ophthalmology and Visual Science, vol. 55, no. 2, pp. 856-864. https://doi.org/10.1167/iovs.13-13033

Disruption of the blood-aqueous barrier and lens abnormalities in mice lacking Lysyl Oxidase-Like 1 (LOXL1). / Wiggs, Janey L.; Pawlyk, Basil; Connolly, Edward; Adamian, Michael; Miller, Joan W.; Pasquale, Louis R.; Haddadin, Ramez I.; Grosskreutz, Cynthia L.; Rhee, Douglas J.; Li, Tiansen.

In: Investigative Ophthalmology and Visual Science, Vol. 55, No. 2, 14.01.2014, p. 856-864.

Research output: Contribution to journalArticle

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T1 - Disruption of the blood-aqueous barrier and lens abnormalities in mice lacking Lysyl Oxidase-Like 1 (LOXL1)

AU - Wiggs, Janey L.

AU - Pawlyk, Basil

AU - Connolly, Edward

AU - Adamian, Michael

AU - Miller, Joan W.

AU - Pasquale, Louis R.

AU - Haddadin, Ramez I.

AU - Grosskreutz, Cynthia L.

AU - Rhee, Douglas J.

AU - Li, Tiansen

PY - 2014/1/14

Y1 - 2014/1/14

N2 - Purpose. 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.

AB - Purpose. 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.

KW - Exfoliation syndrome

KW - Glaucoma

KW - LOXL1

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