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

Objective: To study expression and location of matrix metalloproteinases (M MPs) and tumor necrosis factor a (TNF-alpha) in glaucomatous optic nerve he ads, which are known to be secreted in response to a variety of neuronal in jury. Methods: Four postmortem eyes from patients with primary open-angle glaucom a, 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 t o 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 cell s for MMPs, TNF-alpha,, or TNF-alpha receptor 1 were greater in the glaucom atous optic nerve heads, particularly in eyes with normal-pressure glaucoma compared with age-matched controls. Positive immunostaining was observed i n all regions of the glaucomatous optic nerve heads, but most prominently i n 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-a lpha receptor 1 in the glaucomatous optic nerve head, which suggests increa sed expression of these proteins in glaucoma and thereby implies a role in the tissue remodeling and degenerative changes seen in glaucomatous optic n erve heads. Clinical Relevance: The MMPs and TNF-alpha may be components of astroglial activation that occurs in glaucomatous optic nerve heads. The biological al terations in the expression of these proteins mall play a role in the progr ession of glaucomatous optic neuropathy.