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

Objective: To investigate the effects of topical prostaglandin F-2 alpha-is opropyl ester (PGF(2 alpha)-IE) administration on immunoreactivity of matri x metalloproteinases (MMPs) 1, 2, and 3 within the anterior segment tissues of monkey eyes. Methods: Eight eyes from 4 cynomolgus monkeys were evaluated. One eye from each monkey was treated with 2 mg of PGF(2 alpha)-IE twice daily for 5 days , and intraocular pressure reduction was measured. After fixation and proce ssing, deparaffinized sections of anterior segments were immunostained usin g antibodies to MMP-1 (interstitial collagenase), MMP-2 (gelatinase A), or MMP-3 (stromelysin-1). Optical density along 2 line segments overlying the iris root, ciliary muscle, and adjacent sclera and perpendicular to their l ong axes was measured using imaging densitometry. Results: Compared with the contralateral vehicle-treated eyes, statisticall y significant increases in optical density scores were observed in the iris root, ciliary muscle, and adjacent sclera for all 3 MMPs (P < .01). In the se tissues, MMP-1 immunoreactivity was increased by a mean SD of 89% +/- 16 %, 61% +/- 8%, and 66% +/- 57%, respectively; MMP-2 immunoreactivity by 129 % +/- 53%, 82% +/- 27%, and 267% +/- 210%, respectively; and MMP-3 immuno r eactivity by 207% +/- 84%, 83% +/- 49%, and 726% +/- 500%, respectively. Conclusions: Treatment of monkey eyes with PGF(2 alpha)-IE induces elevatio n 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 incr eased uveoscleral outflow observed with topical prostaglandin treatment. Clinical Relevance: Immunoreactivity of MMPs in tissues of the monkey uveos cleral outflow pathway is increased after topical treatment with PGF(2 alph a)-IE. This response also might be involved in the intraocular pressure-low ering effect of other prostanoids used to treat glaucoma.