April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Extracellular Matrix Proteins Identified in Lens Capsule Pseudoexfoliation Material
Author Affiliations & Notes
  • M. Risco
    Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida
  • G. Munguba
    Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida
  • M. Tapia
    Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida
  • S. K. Bhattacharya
    Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida
  • R. K. Lee
    Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida
  • Footnotes
    Commercial Relationships  M. Risco, None; G. Munguba, None; M. Tapia, None; S.K. Bhattacharya, None; R.K. Lee, None.
  • Footnotes
    Support  NIH K08 EY016775 and American Health Assistance Foundation-Glaucoma grants (RKL), and Research to Prevent Blindness and NIH Core (P30-EY014801) grants (to BPEI).
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 2189. doi:
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      M. Risco, G. Munguba, M. Tapia, S. K. Bhattacharya, R. K. Lee; Extracellular Matrix Proteins Identified in Lens Capsule Pseudoexfoliation Material. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2189.

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

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Abstract

Purpose: : Pseudoexfoliation (PEX) syndrome is associated with the pathologic accumulation of an abnormal fibrillar material, PEX material (PEXM), in the eye. This accumulation of PEXM in the anterior segment causes the most common form of open-angle glaucoma. While the exact composition of PEXM remains unknown, PEXM in the anterior segment of the eye consists of a variety of extracellular matrix (ECM) proteins and elastic fiber structure components. Recently, single nucleotide polymorphisms (SNPs) in exon 1 of the lysyl oxidase-like 1 (LOXL1) gene have been identified as genetic risk factors for PEX. LOXL1 is an important cross-linking enzyme in extracellular matrix metabolism and is associated with elastic fiber formation and stabilization. EMILIN (elastin microfibril interface located protein) -1 is an extracellular matrix glycoprotein that localizes to sites where elastin and microfibrils are in proximity. Galectin-4 belongs to a family of beta-galactoside-binding proteins implicated in modulating cell-cell and cell-matrix interactions. We have identified using molecular techniques that EMILIN and galectin-4 are ECM protein constituents within PEXM, similar to LOXL1.

Methods: : Proteomic analysis of aqueous humor from eyes with PEX was performed using MALDI-TOF. Yeast-2-hybrid (Y2H) protein-protein interaction traps with LOXL1 as bait were conducted using a brain cDNA library. Localization of ECM proteins EMILIN-1, galectin-4, and LOXL-1 to lens capsule PEX material was observed by immunofluorescence. The bioinformatics program GeneGo (www.genego.com) was used for protein-protein interaction analysis.

Results: : Differential proteomic analysis of PEX aqueous humor identified the presence of EMILIN-1. The Y2H protein-protein trap suggested galectin-4 interacts with LOXL1. Immunofluorescence demonstrated the presence of EMILIN-1, LOXL-1, and galectin-4 in pseudoexfoliation material on PEX lens capsule.

Conclusions: : Using proteomics and Y2H, we have identified EMILIN-1 and galectin-4 as ECM molecules, in addition to LOXL1, which are present in PEXM on the lens capsule. Our data suggests that EMILIN-1 and galectin-4, coupled with interactions between LOXL1 and other ECM molecules (such as fibullin-5), result in the orderly assembly of PEX microfibrils. These results add to the growing body of evidence that PEX is an ECM disorder.

Keywords: proteins encoded by disease genes • immunohistochemistry • proteomics 
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