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Increased Matrix Metalloproteinases 1, 2, and 3 in the Monkey Uveoscleral Outflow Pathway After Topical Prostaglandin F₂–Isopropyl Ester Treatment

Dan D. Gaton, MD; Takeshi Sagara, MD, PhD; James D. Lindsey, PhD; B'Ann True Gabelt; Paul L. Kaufman, MD; Robert N. Weinreb, MD

Arch Ophthalmol. 2001;119:1165-1170.

Objective  To investigate the effects of topical prostaglandin F₂–isopropyl ester (PGF₂-IE) administration on immunoreactivity of matrix 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 PGF₂-IE twice daily for 5 days, and intraocular pressure 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 2 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 3 MMPs (P<.01). In these 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 immunoreactivity by 207% ± 84%, 83% ± 49%, and 726% ± 500%, respectively.

Conclusions  Treatment of monkey eyes with PGF₂-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 topical prostaglandin treatment.

Clinical Relevance  Immunoreactivity of MMPs in tissues of the monkey uveoscleral outflow pathway is increased after topical treatment with PGF₂-IE. This response also might be involved in the intraocular pressure–lowering effect of other prostanoids used to treat glaucoma.

From the Glaucoma Center, University of California, San Diego, La Jolla (Drs Gaton, Sagara, Lindsey, and Weinreb); and the Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison (Ms Gabelt and Dr Kaufman). The authors have no proprietary interest in any of the materials used in this study.

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