Glaucomatous tissue stress and the regulation of immune response through glial Toll-like receptor signaling

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

doi:10.1167/iovs.10-5407

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Glaucomatous tissue stress and the regulation of immune response through glial Toll-like receptor signaling

Journal article

Open access

Peer reviewed

Glaucomatous tissue stress and the regulation of immune response through glial Toll-like receptor signaling

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

Investigative ophthalmology & visual science, Vol.51(11), pp.5697-5707

11/2010

DOI: 10.1167/iovs.10-5407

PMCID: PMC3061506

PMID: 20538986

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Abstract

To determine the regulation of immune system activity associated with Toll-like receptor (TLR) signaling in glaucoma. Retinal protein samples obtained from human donor eyes with (n = 10) or without (n = 10) glaucoma were analyzed by a quantitative proteomic approach involving mass spectrometry. Cellular localization of TLR2, -3, and -4 was also determined by immunohistochemical analysis of an additional group of human donor eyes with glaucoma (n = 34) and control eyes (n = 20). In addition, in vitro experiments were performed in rat retinal microglia and astrocytes to determine glial TLR expression and immunoregulatory function after exposure to exogenous heat shock proteins (HSPs) and H(2)O(2)-induced oxidative stress. Proteomic analyses of the human retina detected expression and differential regulation of different TLRs in glaucomatous samples. Parallel to the upregulation of TLR signaling, proteomic findings were also consistent with a prominent increase in the expression of HSPs in glaucoma. Immunohistochemical analysis supported upregulated expression of TLRs on both microglia and astrocytes in the glaucomatous retina. In vitro experiments provided additional evidence that HSPs and oxidative stress upregulate glial TLR and MHC class II expression and cytokine production through TLR signaling and stimulate proliferation and cytokine secretion of co-cultured T cells during antigen presentation. The findings of this study support the upregulation of TLR signaling in human glaucoma, which may be associated with innate and adaptive immune responses. In vitro findings showed that components of glaucomatous tissue stress, including upregulated HSPs and oxidative stress, may initiate the immunostimulatory signaling through glial TLRs.

Immunohistochemistry

Microglia - metabolism

Up-Regulation

Immune System - physiology

Oxidative Stress

Humans

Chromatography, High Pressure Liquid

Rats, Inbred BN

Tandem Mass Spectrometry

Aged, 80 and over

Glaucoma, Open-Angle - metabolism

Toll-Like Receptors - metabolism

Hydrogen Peroxide - toxicity

Astrocytes - drug effects

Microglia - drug effects

Intraocular Pressure

Lymphocyte Activation

Cells, Cultured

Rats

Blotting, Western

Animals

Proteomics

Signal Transduction - physiology

T-Lymphocytes - immunology

Aged

Astrocytes - metabolism

Details

Title: Subtitle: Glaucomatous tissue stress and the regulation of immune response through glial Toll-like receptor signaling
Creators: Cheng Luo - Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, Louisville, Kentucky 40202, USA
Xiangjun Yang
Angela D Kain
David W Powell
Markus H Kuehn
Gülgün Tezel
Resource Type: Journal article
Publication Details: Investigative ophthalmology & visual science, Vol.51(11), pp.5697-5707
DOI: 10.1167/iovs.10-5407
PMID: 20538986
PMCID: PMC3061506
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: 11/2010
Academic Unit: Ophthalmology and Visual Sciences
Record Identifier: 9983979903402771

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