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Identification of LOXL1 protein and Apolipoprotein E as components of surgically isolated pseudoexfoliation material by direct mass spectrometry

Citation

Sharma, S and Chataway, T and Burdon, KP and Jonavicius, L and Klebe, S and Hewitt, AW and Mills, RA and Craig, JE, Identification of LOXL1 protein and Apolipoprotein E as components of surgically isolated pseudoexfoliation material by direct mass spectrometry, Experimental Eye Research: An International Journal Devoted to Scientific Research on The Eye, 89, (4) pp. 479-485. ISSN 0014-4835 (2009) [Refereed Article]

Copyright Statement

Copyright 2009 Elsevier Ltd.

DOI: doi:10.1016/j.exer.2009.05.001

Abstract

Pseudoexfoliation (PEX) syndrome is the commonest cause of secondary glaucoma. Many extracellular matrix proteins and elastic fibre structure components are present in the pathological PEX deposits in the anterior segment of the eye including the anterior lens capsule. Common coding variants in the lysyl oxidase-like 1 (LOXL1) gene, involved in cross-linking elastin, have been reported to be strongly associated with PEX syndrome in various human populations. The mechanism by which the LOXL1 protein contributes to the formation of PEX material is unknown. A comprehensive map of the component proteins of PEX deposits can aid the understanding of disease pathogenesis. The purpose of this study was to identify additional protein constituents of pathological PEX deposits. We employed a novel proteomics approach by performing mass spectrometry on "isolated" PEX material surgically removed from the anterior lens capsule of affected eyes. This approach led to the identification of LOXL1 protein and Apolipoprotein E (ApoE) in PEX material. Previously identified protein constituents, latent-transforming growth factor beta-binding protein-2, complement 3 and clusterin were also detected. Immunohistochemical analysis of lens capsules from affected eyes confirmed the presence of both LOXL1 and ApoE in pathological PEX deposits. ApoE is a novel component of these deposits. This is the first report where a direct analytical approach has led to the identification of LOXL1 in PEX deposits and is consistent with its detection in these deposits by immunolabelling in another recent report. LOXL1 is both genetically associated with PEX syndrome and present in pathological PEX deposits. Hence it clearly has an important and direct role in pathophysiology of the disease. In conclusion, additional as yet unknown components are present in pathological PEX deposits and mass spectrometry of "isolated" PEX material is an effective strategy for their identification.

Item Details

Item Type:Refereed Article
Keywords:cataract; glaucoma; immunohistochemistry; lens capsule; lysyl oxidase-like 1; protein identification; proteomics
Research Division:Medical and Health Sciences
Research Group:Ophthalmology and Optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Hearing, Vision, Speech and Their Disorders
Author:Burdon, KP (Associate Professor Kathryn Burdon)
Author:Hewitt, AW (Dr Alex Hewitt)
ID Code:91091
Year Published:2009
Web of Science® Times Cited:29
Deposited By:Menzies Institute for Medical Research
Deposited On:2014-05-07
Last Modified:2016-11-24
Downloads:0

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