This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (37)  • Contact me when this article is cited  Related Content  • Related article  • Similar articles in this journal  Topic Collections  • Glaucoma  • Articles for Residents  • Alert me on articles by topic  Social Bookmarking   What's this?

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.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati     What's this?

RELATED ARTICLE

Effects of Protein Kinase Inhibitor, HA1077, on Intraocular Pressure and Outflow Facility in Rabbit Eyes
Megumi Honjo, Masaru Inatani, Noriaki Kido, Tatsuya Sawamura, Beatrice Y.-J. T. Yue, Yoshihito Honda, and Hidenobu Tanihara
Arch Ophthalmol. 2001;119(8):1171-1178.
ABSTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Direct Matrix Metalloproteinase Enhancement of Transscleral Permeability
Lindsey et al.
IOVS 2007;48:752-755.
ABSTRACT | FULL TEXT  

Effects of Antiglaucoma Drops on MMP and TIMP Balance in Conjunctival and Subconjunctival Tissue.
Ito et al.
IOVS 2006;47:823-830.
ABSTRACT | FULL TEXT  

Endothelin Antagonism: Effects of FP Receptor Agonists Prostaglandin F2{alpha} and Fluprostenol on Trabecular Meshwork Contractility.
Thieme et al.
IOVS 2006;47:938-945.
ABSTRACT | FULL TEXT  

Modulation of Conventional Outflow Facility by the Adenosine A1 Agonist N6-Cyclohexyladenosine
Crosson et al.
IOVS 2005;46:3795-3799.
ABSTRACT | FULL TEXT  

Prostaglandin FP Agonists Alter Metalloproteinase Gene Expression in Sclera
Weinreb et al.
IOVS 2004;45:4368-4377.
ABSTRACT | FULL TEXT  

Effect of Latanoprost on Outflow Facility in the Mouse
Crowston et al.
IOVS 2004;45:2240-2245.
ABSTRACT | FULL TEXT  

Comparison of Prostaglandin F2{alpha}, Bimatoprost (Prostamide), and Butaprost (EP2 Agonist) on Cyr61 and Connective Tissue Growth Factor Gene Expression
Liang et al.
J. Biol. Chem. 2003;278:27267-27277.
ABSTRACT | FULL TEXT  

Expression and distribution of matrix metalloproteinases and their inhibitors in the human iris and ciliary body
Lan et al.
Br. J. Ophthalmol. 2003;87:208-211.
ABSTRACT | FULL TEXT  

Latanoprost's Effects on TIMP-1 and TIMP-2 Expression in Human Ciliary Muscle Cells
Anthony et al.
IOVS 2002;43:3705-3711.
ABSTRACT | FULL TEXT  

Detection of Prostaglandin EP1, EP2, and FP Receptor Subtypes in Human Sclera
Anthony et al.
IOVS 2001;42:3182-3186.
ABSTRACT | FULL TEXT