April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
Role of Lox(l) in the Eye After Laser Photocoagulation in a Mouse Model for Age Related Macular Degeneration
Author Affiliations & Notes
  • E. Vandewalle
    Laboratory of Ophthalmology,
    K.U.Leuven, Leuven, Belgium
    Department of Ophthalmology, University Hospitals Leuven, Leuven, Belgium
  • T. Van Bergen
    Laboratory of Ophthalmology,
    K.U.Leuven, Leuven, Belgium
  • S. Van de Veire
    Laboratory of Ophthalmology,
    K.U.Leuven, Leuven, Belgium
    Department of Ophthalmology, University Hospitals Leuven, Leuven, Belgium
  • L. Moons
    Department of Biology,
    K.U.Leuven, Leuven, Belgium
  • S. Fevery
    Department of Experimental Transplantation,
    K.U.Leuven, Leuven, Belgium
  • V. Smith
    Arresto Biosciences, Palo Alto, Iowa
  • S. Ogg
    Arresto Biosciences, Palo Alto, Iowa
  • I. Stalmans
    Laboratory of Ophthalmology,
    K.U.Leuven, Leuven, Belgium
    Department of Ophthalmology, University Hospitals Leuven, Leuven, Belgium
  • Footnotes
    Commercial Relationships  E. Vandewalle, Arresto Biosciences, F; T. Van Bergen, Arresto Biosciences, F; S. Van de Veire, Arresto Biosciences, F; L. Moons, None; S. Fevery, Arresto Biosciences, F; V. Smith, Arresto Biosciences, F; S. Ogg, Arresto Biosciences, F; I. Stalmans, Arresto Biosciences, F.
  • Footnotes
    Support  Arresto Biosciences, Palo Alto, United States
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 771. doi:
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    • Get Citation

      E. Vandewalle, T. Van Bergen, S. Van de Veire, L. Moons, S. Fevery, V. Smith, S. Ogg, I. Stalmans; Role of Lox(l) in the Eye After Laser Photocoagulation in a Mouse Model for Age Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2009;50(13):771.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Lysyl oxidase (LOX) and lysyl oxidase-like proteins (LOXL) are known to be involved in the cross-linking of collagen and elastin in the extracellular space. Therefore, these proteins play a major role in the process of fibrosis. This study was designed to elucidate the role of LOX and LOXL2 in inflammation and fibrosis after choroidal neovascularization (CNV).

Methods: : CNV was induced by placing 3 laser spots at 9, 12 and 3 o’clock position (50µm, 0.05 s and 400mW) in 8 to 10 weeks old C75Bl/6 mice. Mice were sacrificed 4, 7, 14 and 28 days after laser. LOX and LOXL2 expression in choroid and retina was analyzed by using quantitative real time RT-PCR. Inflammation was studied by an immunohistochemical staining for CD45; fibrosis was evaluated by a Sirius Red and Trichrome staining.

Results: : Both LOX and LOXL2 were significantly increased in choroid and retina of lasered mice. LOX was 3.2, 1.75, 1.3 and 2 times upregulated on day 4, 7, 14 and 28 after laser compared to the relative expression of LOX in non-lasered eyes (P<0.05). LOXL2 was 1.6, 1.3, 1.1 and 1.5 times upregulated on day 4, 7, 14 and 28 after laser versus LOXL2 expression in non-lasered eyes (P<0.05) On day 4 after laser, the number of inflammatory cells was increased by 11% compared to the other time-points. Both Sirius Red and Thrichrome staining showed a significant increase of collagen deposition in the choroid on day 14 (34%) and 28 (38%) after laser compared to day 4 (7%) and 7 (14%) (P<0.05).

Conclusions: : The upregulation of LOX and LOXL2 suggests that these molecules play a role in the process of inflammation and fibrosis after the induction of choroidal neovascularization. This finding can open new perspectives in the treatment of age-related macular degeneration by inhibiting LOX and LOXL.

Keywords: choroid: neovascularization • age-related macular degeneration • inflammation 
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