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Abstract #6485 Published in IGR 3-2

Increased matrix metalloproteinases 1, 2, and 3 in the monkey uveoscleral outflow pathway after topical prostaglandin F-isopropyl ester treatment

Gaton DD; Sagara T; Lindsey JD; True Gabelt BA; Kaufman PL; Weinreb RN
Archives of Ophthalmology 2001; 119: 1165-1170


OBJECTIVE: To investigate the effects of topical prostaglandin F-isopropyl ester (PGF-IE) administration on the immunoreactivity of matrix metalloproteinases (MMPs) 1, 2, and 3 within the anterior segment tissues of monkey eyes. METHODS: Eight eyes from four cynomolgus monkeys were evaluated. One eye from each monkey was treated with 2 mg of PGF-IE twice daily for five days, and intraocular pressure (IOP) reduction was measured. After fixation and processing, deparaffinized sections of anterior segments were immunostained using antibodies to MMP-1 (interstitial collagenase), MMP-2 (gelatinase A), or MMP-3 (stromelysin-1). Optical density along two-line segments overlying the iris root, ciliary muscle, and adjacent sclera and perpendicular to their long axes was measured using imaging densitometry. RESULTS: Compared with the contralateral vehicle-treated eyes, statistically significant increases in optical density scores were observed in the iris root, ciliary muscle, and adjacent sclera for all three MMPs (p < 0.01). In these tissues, MMP-1 immunoreactivity was increased by a mean ± of 89 ± 16%, 61 ± 8%, and 66 ± 57%, respectively; MMP-2 immunoreactivity by 129 ± 53%, 82 ± 27%, and 267 ± 210%, respectively; and MMP-3 immunoreactivity by 207 ± 84, 83 ± 49, and 726 ± 500%, respectively. CONCLUSIONS: Treatment of monkey eyes with PGF-IE induces elevation of MMP-1, MMP-2, and MMP-3 in tissues of the uveoscleral outflow pathway. These increases suggest that MMPs might play an important role in the increased uveoscleral outflow observed with optical prostaglandin treatment. CLINICAL RELEVANCE: Immunoreactivity of MMPs in tissues of the monkey uveoscleral outflow pathway is increased after topical treatment with PGF-IE. This response might also be involved in the IOP-lowering effect of other prostanoids used to treat glaucoma.

Dr D.D. Gaton, Glaucoma Center, University of California, San Diego, La Jolla, CA, USA


Classification:

11.4 Prostaglandins (Part of: 11 Medical treatment)



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