April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Subtle Inflammatory Processes Are Involved in the Initiation of the Abnormal Matrix Process in Pseudoexfoliation (PEX) Syndrome/Glaucoma
Author Affiliations & Notes
  • M. Zenkel
    Department of Ophthalmology, University Erlangen Nuernberg, Erlangen, Germany
  • F. E. Kruse
    Department of Ophthalmology, University Erlangen Nuernberg, Erlangen, Germany
  • K. Bitterer
    Department of Ophthalmology, University Erlangen Nuernberg, Erlangen, Germany
  • A. Jünemann
    Department of Ophthalmology, University Erlangen Nuernberg, Erlangen, Germany
  • U. Schlötzer-Schrehardt
    Department of Ophthalmology, University Erlangen Nuernberg, Erlangen, Germany
  • Footnotes
    Commercial Relationships  M. Zenkel, None; F.E. Kruse, None; K. Bitterer, None; A. Jünemann, None; U. Schlötzer-Schrehardt, None.
  • Footnotes
    Support  DFG Grant SFB539
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 6121. doi:
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      M. Zenkel, F. E. Kruse, K. Bitterer, A. Jünemann, U. Schlötzer-Schrehardt; Subtle Inflammatory Processes Are Involved in the Initiation of the Abnormal Matrix Process in Pseudoexfoliation (PEX) Syndrome/Glaucoma. Invest. Ophthalmol. Vis. Sci. 2010;51(13):6121.

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

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Abstract

Purpose: : The dysregulated expression of inflammatory markers, such as interleukin (IL)-1, IL-6, and IL-8, has been implicated in the initiation of fibrosis and in the pathophysiology of glaucoma. To determine the role of IL-6 in PEX syndrome/glaucoma (PEXS/PEXG), we examined the expression and functional significance of IL-6 in PEX and control eyes.

Methods: : Patients and donor eyes were classified as early or late stage PEXS according to the amount of (bio-)microscopically visible ocular PEX material. Aqueous IL-6 levels in patients with cataract, early and late stages of PEXS, and PEXG were analyzed by ELISA (n=12 each group). IL-6 and IL-6 receptor expression in ocular tissues from normal, early PEX, late PEX, and PEXG donors was analyzed by immunohistochemistry and real-time PCR (n=6), and the phosphorylation of STAT-3 was monitored by Western blot (n=4). Real-time PCR was used to study the regulation of IL-6 and its effect on transforming growth factor (TGF)-ß1, fibrillin-1, and latent TGF-ß binding protein (LTBP-1) in nonpigmented ciliary epithelial (NPE) cells in vitro.

Results: : Early stages of PEXS were characterized by elevated aqueous IL-6 levels (2.5-fold; p<0.005) and increased IL-6 mRNA expression (2-fold; p<0.001) in anterior segment tissues as compared to controls, whereas late stages of PEXS/G did not differ significantly. IL-6 and IL-6 receptor could be mainly localized to walls of iris vessels and to the ciliary epithelium. The ratio of phospho-STAT-3 to STAT-3 in iridal and ciliary tissues was increased in eyes with early PEXS, as compared with normal donors and late PEXS/G stages (2-fold; p<0.01). IL-6 was upregulated in NPE cells in response to hypoxia (2% O2) or oxidative (50 µM H2O2) stress (5-fold; p<0.001), and induced the expression of TGF-ß1 and main components of PEX material, such as fibrillin-1 and LTBP-1 (3-fold; p<0.001).

Conclusions: : These findings support a role for a stress-induced, temporally restricted subclinical inflammation, reflected by increased aqueous IL-6 levels and the activation of the STAT-3 pathway, in the onset of the fibrotic matrix process characteristic of PEX syndrome.

Keywords: extracellular matrix • cytokines/chemokines • gene/expression 
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