Document Detail


Oxidative stress and the regulation of complement activation in human glaucoma.
MedLine Citation:
PMID:  20484586     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: As part of ongoing studies on proteomic alterations during glaucomatous neurodegeneration, this study focused on the complement system.
METHODS: Human retinal protein samples obtained from donor eyes with (n = 10) or without (n = 10) glaucoma were analyzed by a quantitative proteomic approach using mass spectrometry. Cellular localization of protein expression for different complement components and regulators were also determined by immunohistochemical analysis of an additional group of human donor eyes with glaucoma (n = 34) compared with age-matched control eyes without glaucoma (n = 20). In addition, to determine the regulation of complement factor H (CFH) by oxidative stress, in vitro experiments were performed using rat retinal cell cultures incubated in the presence and absence of an oxidant treatment.
RESULTS: Proteomic analysis detected the expression and differential regulation of several complement components in glaucomatous samples, which included proteins involved in the classical and the lectin pathways of complement activation. In addition, several complement regulatory proteins were detected in the human retinal proteome, and glaucomatous samples exhibited a trend toward downregulation of CFH expression. In vitro experiments revealed that oxidative stress, which was also prominently detectable in the glaucomatous human retinas, downregulated CFH expression in retinal cells.
CONCLUSIONS: These findings expand the current knowledge of complement activation by presenting new evidence in human glaucoma and support that despite important roles in tissue cleaning and healing, a potential deficiency in intrinsic regulation of complement activation, as is evident in the presence of oxidative stress, may lead to uncontrolled complement attack with neurodestructive consequences.
Authors:
Gülgün Tezel; Xiangjun Yang; Cheng Luo; Angela D Kain; David W Powell; Markus H Kuehn; Henry J Kaplan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-05-19
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  51     ISSN:  1552-5783     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-09-29     Completed Date:  2010-10-19     Revised Date:  2014-09-15    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5071-82     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Aged
Aged, 80 and over
Animals
Blotting, Western
Cells, Cultured
Complement Activation / drug effects,  physiology*
Complement System Proteins / metabolism*
Down-Regulation
Fluorescent Antibody Technique, Indirect
Glaucoma, Open-Angle / metabolism*
Humans
Hydrogen Peroxide / pharmacology
Intraocular Pressure
Oxidative Stress*
Proteomics
Rats
Retina / drug effects,  metabolism
Retinal Ganglion Cells / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Tandem Mass Spectrometry
Tissue Donors
Grant Support
ID/Acronym/Agency:
1R01 EY017131/EY/NEI NIH HHS; 2R01 EY013813/EY/NEI NIH HHS; R01 EY013813/EY/NEI NIH HHS; R01 EY013813-01A2/EY/NEI NIH HHS; R01 EY013813-02/EY/NEI NIH HHS; R01 EY013813-03/EY/NEI NIH HHS; R01 EY013813-04/EY/NEI NIH HHS; R01 EY013813-05A1/EY/NEI NIH HHS; R01 EY013813-06/EY/NEI NIH HHS; R01 EY013813-07/EY/NEI NIH HHS; R01 EY013813-08/EY/NEI NIH HHS; R01 EY013813-09/EY/NEI NIH HHS; R01 EY017131/EY/NEI NIH HHS; R01 EY017131-01A2/EY/NEI NIH HHS; R01 EY017131-02/EY/NEI NIH HHS; R01 EY017131-03/EY/NEI NIH HHS; R01 EY019485/EY/NEI NIH HHS; R24 EY015636/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
9007-36-7/Complement System Proteins; BBX060AN9V/Hydrogen Peroxide
Comments/Corrections

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