NDLI: Genotype-correlated expression of lysyl oxidase-like 1 in ocular tissues of patients with pseudoexfoliation syndrome/glaucoma and normal patients.

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Genotype-correlated expression of lysyl oxidase-like 1 in ocular tissues of patients with pseudoexfoliation syndrome/glaucoma and normal patients.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Schlötzer-Schrehardt, Ursula Pasutto, Francesca Sommer, Pascal Hornstra, Ian Kruse, Friedrich E. Naumann, Gottfried O. H. Reis, André Zenkel, Matthias
Description	Country affiliation: Germany Author Affiliation: Schlötzer-Schrehardt U ( Department of Ophthalmology, University of Erlangen-Nürnberg, Erlangen, Germany. ursula.schloetzer-schrehardt@uk-erlangen.de)
Abstract	Pseudoexfoliation (PEX) syndrome is a generalized disease of the extracellular matrix and the most common identifiable cause of open-angle glaucoma. Two single nucleotide polymorphisms in the lysyl oxidase-like 1 (LOXL1) gene (rs1048661 and rs3825942) have been recently identified as strong genetic risk factors for both PEX syndrome and PEX glaucoma. Here we investigated the expression and localization of LOXL1, LOXL2, and lysyl oxidase (LOX) in tissues of PEX syndrome/glaucoma patients and controls in correlation with their individual single nucleotide polymorphism genotypes and stages of disease. LOXL1 ocular expression was reduced by approximately 20% per risk allele of rs1048661, whereas risk alleles of rs3825942, which were highly overrepresented in PEX cases, did not affect LOXL1 expression levels. Irrespective of the individual genotype, LOXL1 expression was significantly increased in early PEX stages but was decreased in advanced stages both with and without glaucoma compared with controls, whereas LOX and LOXL2 showed no differences between groups. LOXL1 was also found to be a major component of fibrillar PEX aggregates in both intra- and extraocular locations and to co-localize with various elastic fiber components. These findings provide evidence for LOXL1 involvement in the initial stages of abnormal fibrogenesis in PEX tissues. Alterations of LOXL1 activation, processing, and/or substrate specificity may contribute to the abnormal aggregation of elastic fiber components into characteristic PEX fibrils.
File Format	HTM / HTML
ISSN	00029440
e-ISSN	15252191
DOI	10.2353/ajpath.2008.080535
Journal	The American Journal of Pathology
Issue Number	6
Volume Number	173
Language	English
Publisher	Elsevier (on behalf of the American Society for Investigative Pathology)
Publisher Date	2008-12-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Glaucoma Research Support, Non-u.s. Gov't Amino Acid Oxidoreductases Eye Lens, Crystalline Extracellular Matrix Proteins Ultrastructure Genetics Exfoliation Syndrome Isoenzymes Protein-lysine 6-oxidase Genotype Discipline Pathology Tropoelastin Metabolism Genetic Predisposition To Disease Physiopathology Pathology Animals Microfilament Proteins Polymorphism, Single Nucleotide Enzymology
Content Type	Text
Resource Type	Article
Subject	Pathology and Forensic Medicine

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Genotype-Correlated Expression of Lysyl Oxidase-Like 1 in Ocular Tissues of Patients with Pseudoexfoliation Syndrome/Glaucoma and Normal Patients

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Genotype-correlated expression of lysyl oxidase-like 1 in ocular tissues of patients with pseudoexfoliation syndrome/glaucoma and normal patients.

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