Activation of a tissue-specific stress response in the aqueous outflow pathway of the eye defines the glaucoma disease phenotype

N. Wang, S. K. Chintala, M. E. Fini, J. S. Schuman

    Research output: Contribution to journalArticlepeer-review

    Abstract

    The glaucomas are a group of optic neuropathies comprising the leading cause of irreversible blindness worldwide. Elevated intraocular pressure due to a reduction in normal aqueous outflow is a major causal risk factor. We found that endothelial leukocyte adhesion molecule-1 (ELAM-1), the earliest marker for the atherosclerotic plaque in the vasculature, was consistently present on trabecular meshwork (TM) cells in the outflow pathways of eyes with glaucomas of diverse etiology. We determined expression of ELAM-1 to be controlled by activation of an interleukin-1 (IL-1) autocrine feedback loop through transcription factor NF-κB, and activity of this signaling pathway was shown to protect TM cells against oxidative stress. These findings characterize a protective stress response specific to the eye's aqueous outflow pathways and provide the first known diagnostic indicator of glaucomatous TM cells. They further indicate that common mechanisms contribute to the pathophysiology of the glaucomas and vascular diseases.

    Original languageEnglish (US)
    Pages (from-to)304-309
    Number of pages6
    JournalNature Medicine
    Volume7
    Issue number3
    DOIs
    StatePublished - 2001

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)

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