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)--isopropyl ester (PGF(2 alpha)-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 PGF(2 alpha)-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 PGF(2 alpha)-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.


CONCLUSIONS
Immunoreactivity of MMPs in tissues of the monkey uveoscleral outflow pathway is increased after topical treatment with PGF(2 alpha)-IE. This response also might be involved in the intraocular pressure--lowering effect of other prostanoids used to treat glaucoma.
Gaton
D D
DD
Glaucoma Center, University of California, San Diego, La Jolla, CA 92093-0946, USA.
Sagara
T
T
Lindsey
J D
JD
Gabelt
B T
BT
Kaufman
P L
PL
Weinreb
R N
RN
D000287:Administration, Topical; D000818:Animals; D000869:Anterior Eye Segment / Q000187:drug effects* / Q000201:enzymology; D002924:Ciliary Body / Q000187:drug effects / Q000201:enzymology; D015237:Dinoprost / Q000008:administration & dosage* / Q000031:analogs & derivatives; D007124:Immunoenzyme Techniques; D007429:Intraocular Pressure / Q000187:drug effects; D007498:Iris / Q000187:drug effects / Q000201:enzymology; D008252:Macaca fascicularis; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D009130:Muscle, Smooth / Q000187:drug effects / Q000201:enzymology; D009883:Ophthalmic Solutions / Q000008:administration & dosage; D012590:Sclera / Q000187:drug effects* / Q000201:enzymology; D014602:Uvea / Q000187:drug effects* / Q000201:enzymology
D009883:Ophthalmic Solutions; C041158:prostaglandin F2 isopropyl ester; D015237:Dinoprost; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020781:Matrix Metalloproteinase 1