Oxidative stress and the regulation of complement activation in human glaucoma

Gülgün Tezel; Xiangjun Yang; Cheng Luo; Angela D Kain; David W Powell; Markus H Kuehn; Henry J Kaplan

doi:10.1167/iovs.10-5289

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Oxidative stress and the regulation of complement activation in human glaucoma

Journal article

Open access

Peer reviewed

Oxidative stress and the regulation of complement activation in human glaucoma

Gülgün Tezel, Xiangjun Yang, Cheng Luo, Angela D Kain, David W Powell, Markus H Kuehn and Henry J Kaplan

Investigative ophthalmology & visual science, Vol.51(10), pp.5071-5082

10/2010

DOI: 10.1167/iovs.10-5289

PMCID: PMC3066595

PMID: 20484586

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Abstract

As part of ongoing studies on proteomic alterations during glaucomatous neurodegeneration, this study focused on the complement system. 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. 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. 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.

Retina - drug effects

Retina - metabolism

Oxidative Stress

Intraocular Pressure

Down-Regulation

Humans

Cells, Cultured

Hydrogen Peroxide - pharmacology

Rats

Retinal Ganglion Cells - metabolism

Reverse Transcriptase Polymerase Chain Reaction

Blotting, Western

Complement System Proteins - metabolism

Tandem Mass Spectrometry

Animals

Proteomics

Aged, 80 and over

Glaucoma, Open-Angle - metabolism

Aged

Tissue Donors

Complement Activation - drug effects

Fluorescent Antibody Technique, Indirect

Complement Activation - physiology

Details

Title: Subtitle: Oxidative stress and the regulation of complement activation in human glaucoma
Creators: Gülgün Tezel - Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, Louisville, Kentucky, USA. gulgun.tezel@louisville.edu
Xiangjun Yang
Cheng Luo
Angela D Kain
David W Powell
Markus H Kuehn
Henry J Kaplan
Resource Type: Journal article
Publication Details: Investigative ophthalmology & visual science, Vol.51(10), pp.5071-5082
DOI: 10.1167/iovs.10-5289
PMID: 20484586
PMCID: PMC3066595
NLM abbreviation: Invest Ophthalmol Vis Sci
ISSN: 0146-0404
eISSN: 1552-5783
Publisher: United States
Grant note: R01 EY019485 / NEI NIH HHS R01 EY017131-03 / NEI NIH HHS 2R01 EY013813 / NEI NIH HHS R01 EY013813-01A2 / NEI NIH HHS R01 EY013813-08 / NEI NIH HHS R01 EY013813-07 / NEI NIH HHS R01 EY013813-05A1 / NEI NIH HHS R01 EY013813-03 / NEI NIH HHS R01 EY017131 / NEI NIH HHS R24 EY015636 / NEI NIH HHS R01 EY017131-02 / NEI NIH HHS 1R01 EY017131 / NEI NIH HHS R01 EY013813-09 / NEI NIH HHS R01 EY013813-06 / NEI NIH HHS R01 EY013813-04 / NEI NIH HHS R01 EY017131-01A2 / NEI NIH HHS R01 EY013813-02 / NEI NIH HHS R01 EY013813 / NEI NIH HHS
Language: English
Date published: 10/2010
Academic Unit: Ophthalmology and Visual Sciences
Record Identifier: 9983980029302771

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