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Topical Prostaglandin F₂ Treatment Reduces Collagen Types I, III, and IV in the Monkey Uveoscleral Outflow Pathway

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

Arch Ophthalmol. 1999;117:794-801.

Background  Topical prostaglandin F₂ isopropyl ester increases uveoscleral outflow in monkeys and humans.

Objective  To investigate the effects of prostaglandin F₂ isopropyl ester with topical administration on collagen types I, III, and IV within the anterior segment tissue of monkey eyes.

Methods  Eight eyes of 4 cynomolgus monkeys were evaluated. One eye of each monkey was treated with 2 µg of prostaglandin F₂ isopropyl ester twice daily for 5 days, and intraocular pressure reduction was confirmed. These eyes were fixed in methacarn, and paraffin sections were immunostained using antibodies to collagen types I, III, or IV. To measure staining intensity, optical density (OD) was determined using 2-dimensional imaging densitometry. Mean OD scores along line segments placed over the ciliary muscle were determined.

Results  Mean ±SD OD scores for collagen types I, III, and IV were less in the ciliary muscle of prostaglandin-treated eyes than in vehicle-treated eyes by 52% ± 7%, 45% ± 6%, and 45% ± 5%, respectively. In the sclera adjacent to the ciliary body, mean OD scores for collagen types I and III were less in prostaglandin-treated eyes, by 43% ± 32% and 45% ± 13%, respectively. The scleral stroma was minimally immunoreactive for collagen type IV. All differences were significant by the paired Student t test (P<.05).

Conclusions  This study shows reduced collagen types I, III, and IV immunoreactivity in the ciliary muscle and adjacent sclera following topical prostaglandin F₂ isopropyl ester treatment. These reductions may contribute to the increased uveoscleral outflow observed with topical prostaglandin treatment.

Clinical Relevance  The cellular mechanism by which certain prostaglandins lower intraocular pressure is not known. The present study provides immunohistochemical data demonstrating that intraocular pressure reduction that occurs with topical prostaglandin F₂ is associated with a reduction of collagens within the uveoscleral outflow pathway.

From the Department of Ophthalmology, University of California, San Diego, La Jolla (Drs Sagara, Gaton, Lindsey, and Weinreb); and Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison (Ms Gabelt and Dr Kaufman).

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