May 2004
Volume 45, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2004
Proteomic Approaches to the Etiology of Glaucoma
S.K. Bhattacharya; K.A. West; J.S. Crabb; N.G. Robertson; J. Sun; E.J. Rockwood; S.D. Smith; C.C. Morton; J.W. Crabb
Author Affiliations & Notes
  • S.K. Bhattacharya
    Ophthalmic Research,
    Cole Eye Institute Cleveland Clinic Foundation, Cleveland, OH
  • K.A. West
    Ophthalmic Research,
    Cole Eye Institute Cleveland Clinic Foundation, Cleveland, OH
  • J.S. Crabb
    Ophthalmic Research,
    Cole Eye Institute Cleveland Clinic Foundation, Cleveland, OH
  • N.G. Robertson
    Brigham and Women's Hospital, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
  • J. Sun
    Ophthalmic Research,
    Cole Eye Institute Cleveland Clinic Foundation, Cleveland, OH
  • E.J. Rockwood
    Glaucoma,
    Cole Eye Institute Cleveland Clinic Foundation, Cleveland, OH
  • S.D. Smith
    Glaucoma,
    Cole Eye Institute Cleveland Clinic Foundation, Cleveland, OH
  • C.C. Morton
    Brigham and Women's Hospital, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
  • J.W. Crabb
    Ophthalmic Research,
    Cole Eye Institute Cleveland Clinic Foundation, Cleveland, OH
  • Footnotes
    Commercial Relationships  S.K. Bhattacharya, None; K.A. West, None; J.S. Crabb, None; N.G. Robertson, None; J. Sun, None; E.J. Rockwood, None; S.D. Smith, None; C.C. Morton, None; J.W. Crabb, None.
  • Footnotes
    Support  Supported in part by NIH grants EY06603, EY14239, a Research Center Grant from The Foundation Fighti
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 4560. doi:
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      S.K. Bhattacharya, K.A. West, J.S. Crabb, N.G. Robertson, J. Sun, E.J. Rockwood, S.D. Smith, C.C. Morton, J.W. Crabb; Proteomic Approaches to the Etiology of Glaucoma . Invest. Ophthalmol. Vis. Sci. 2004;45(13):4560.

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Abstract

Abstract: : Purpose:To identify trabecular meshwork proteins and protein modifications associated with the pathology of primary open angle glaucoma. Methods:Trabecular meshwork (TM) tissues were obtained from normal cadavers and from glaucoma patients undergoing trabeculectomy. TM was subjected to SDS–PAGE, proteins were excised, digested in situ with trypsin and identified by capillary LC MS/MS. Western analyses for oxidative protein modification were performed with antibodies to carboxyethylpyrrole (CEP), hydroxynoneal (HNE) and argpyrimidine (AGEs). Western and immunohistochemical analysis for cochlin were performed with chicken polyclonal anti–Cochlin antibody. Results:Proteomic analyses of TM (n = 12 donors) have identified 370 proteins. Proteins known to be present in the TM and found in this preliminary study include TIGR or myocilin, myosin, apoliporotein E, optimedin, laminin, decorin, and collagens I, IV and XVIII. Among the 57 proteins only observed in glaucomatous TM, myocilin was identified in 3/6 and cochlin in 9/10 donor tissues. Cochlin was present in glaucomatous tissue in two isoforms of ∼50 and ∼66 KDa and associated with apparent acellular TM deposits based on immunological analyses. Cochlin was not detected in normal TM tissue. Western analyses revealed HNE immunoreactivity associated with 4/4 glaucomatous TM but in none of the normal TM analyzed (0/4). Conclusions:Cochlin is associated with a human nonsyndromic deafness and vestibular disorder, designated DFNA9. Based on its presence in glaucomatous TM but not normal TM, cochlin may also be associated with pathogenic mechanisms of glaucoma. Preliminary immunohistochemistry suggests that cochlin may be involved in the formation of extracellular deposits in the TM that could impede aqueous flow. Oxidative protein modifications from HNE were only observed in glaucomatous TM and may also contribute to extracellular deposit formation.

Keywords: proteomics • outflow: trabecular meshwork • protein modifications–post translational 
© 2004, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2024 Association for Research in Vision and Ophthalmology.
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