Matrix metalloproteinases and tumor necrosis factor alpha in glaucomatous optic nerve head.

ABSTRACT

OBJECTIVE: To study expression and location of matrix metalloproteinases (MMPs) and tumor necrosis factor alpha (TNF-alpha) in glaucomatous optic nerve heads, which are known to be secreted in response to a variety of neuronal injury. METHODS: Four postmortem eyes from patients with primary open-angle glaucoma, 7 eyes from patients with normal-pressure glaucoma, and 4 eyes from age-matched normal donors were studied by immunohistochemistry. The sections of the optic nerve heads were examined after immunostaining with antibodies to MMPs (MMP-1, MMP-2, and MMP-3), TNF-alpha, or TNF-alpha receptor 1. RESULTS: The intensity of the immunostaining and the number of stained cells for MMPs, TNF-alpha, or TNF-alpha receptor 1 were greater in the glaucomatous optic nerve heads, particularly in eyes with normal-pressure glaucoma compared with age-matched controls. Positive immunostaining was observed in all regions of the glaucomatous optic nerve heads, but most prominently in the postlaminar region. Immunostaining was observed mainly in glial cells and their processes around the axons and blood vessels and in pial septae. CONCLUSION: There is increased immunostaining for MMPs, TNF-alpha and TNF-alpha receptor 1 in the glaucomatous optic nerve head, which suggests increased expression of these proteins in glaucoma and thereby implies a role in the tissue remodeling and degenerative changes seen in glaucomatous optic nerve heads. CLINICAL RELEVANCE The MMPs and TNF-alpha may be components of astroglial activation that occurs in glaucomatous optic nerve heads. The biological alterations in the expression of these proteins may play a role in the progression of glaucomatous optic neuropathy.