Browse

Increased choroidal neovascularization following laser induction in mice lacking lysyl oxidase-like 1

Cited 39 time in Web of Science Cited 46 time in Scopus
Authors
Yu, Hyeong Gon; Liu, Xiaoqing; Kiss, Szilard; Connolly, Edward; Gragoudas, Evangelos S; Michaud, Norman A; Bulgakov, Oleg V; Adamian, Michael; DeAngelis, Margaret M; Miller, Joan W; Li, Tiansen; Kim, Ivana K
Issue Date
2008-02-26
Publisher
Association for Research in Vision and Ophthalmology (ARVO)
Citation
Invest Ophthalmol Vis Sci. 2008;49(6):2599-2605
Keywords
Amino Acid Oxidoreductases/*physiologyAnimalsBruch Membrane/*enzymology/ultrastructureChoroidal Neovascularization/*enzymology/etiology/*physiopathologyElastic Tissue/*enzymology/ultrastructureElastin/metabolismEnzyme-Linked Immunosorbent AssayFemaleFluorescein AngiographyFluorescent Antibody Technique, IndirectImmunoblotting*Laser CoagulationMaleMatrix Metalloproteinases/metabolismMiceMice, Inbred C57BLMice, KnockoutMicroscopy, ImmunoelectronVascular Endothelial Growth Factor A/metabolism
Abstract
PURPOSE: Age-related degradation of the elastic lamina in Bruch's membrane may have a permissive effect on the growth of choroidal neovascularization (CNV). This study investigated the influence of defective elastic fiber maintenance in the development of laser-induced CNV. METHODS: A mouse lacking lysyl oxidase-like (LOXL)-1, an enzyme essential for elastin polymerization, was studied. The morphologic characteristics of the elastic lamina within Bruch's membrane were examined in mutant and wild-type (WT) eyes. Laser-induced CNV was evaluated by fluorescein angiography and choroidal flat mounts. Immunohistochemistry for elastin was performed on the CNV lesions, and vascular endothelial growth factor (VEGF) levels were determined by ELISA. Soluble elastin and matrix metalloproteinase (MMPs) levels were also analyzed by immunoblotting. RESULTS: The elastic lamina of Bruch's membrane in the LOXL1-deficient mice was fragmented and less continuous than in the WT controls. The mutant mice showed increased levels of soluble elastin peptides and reduced elastin polymer deposition in neovascular membranes. Significantly larger CNV with greater leakage on fluorescein angiography developed in mutant mice. VEGF levels in the RPE/choroid were higher in the knockout mice on days 7 and 14 after laser (P < 0.05). MT1-MMP (MMP14) was also elevated after laser in the LOXL1 mutant eyes compared to the WT controls. CONCLUSIONS: These results show that a systemic defect in elastic fiber deposition affects Bruch's membrane integrity and leads to more aggressive CNV growth. The latter may be partially mediated by abnormal signaling from the accumulation of soluble elastin peptides.
ISSN
0146-0404 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18296663

http://www.iovs.org/cgi/reprint/49/6/2599.pdf

http://hdl.handle.net/10371/68193
DOI
https://doi.org/10.1167/iovs.07-1508
Files in This Item:
There are no files associated with this item.
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Ophthalmology (안과학전공)Journal Papers (저널논문_안과학전공)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse