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Baohe Tian, MD; Cameron Millar, PhD; Paul L. Kaufman, MD; Alexander Bershadsky, PhD; Eitan Becker, PhD; Benjamin Geiger, PhD

Arch Ophthalmol. 1998;116:1070-1077.

Objectives  To determine the effects of H-7 on (1) iris and ciliary muscles (CMs) in living monkeys; (2) isolated monkey CM strips; (3) actomyosin contractility in cultured Swiss 3T3 cells.

Methods  (1) Pupillary diameter (calipers) and accommodation (refractometer) in living monkeys were measured after topical, intracameral, or intravitreal administration of H-7 followed by systemic pilocarpine hydrochloride. (2) Pilocarpine-induced contraction of isolated monkey CM strips following administration of H-7 was measured in a perfusion chamber. (3) Actomyosin contractility in Swiss 3T3 cells cultured on thin silicone rubber film was determined by measuring cell-induced film wrinkles before and after administration of H-7.

Results  Topical H-7 prevented anesthesia-induced miosis but did not affect resting refraction. Intracameral or intravitreal H-7 dilated the pupil and inhibited miotic but not accommodative responses to pilocarpine. H-7 inhibited pilocarpine-induced contraction of isolated monkey CM strips and reduced Swiss 3T3 cell contraction.

Conclusions  H-7 inhibits actin-based contractility in non-muscle cells and in monkey iris sphincter and CM. Under our in vivo experimental conditions, the effect on the iris predominates over that on the CM.

From the Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison (Drs Tian, Millar, and Kaufman), the Wisconsin Regional Primate Research Center (Dr Kaufman), Madison; and the Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel (Drs Bershadsky, Becker, and Geiger). University of Wisconsin and Weizmann Institute of Science have filed a related patent application; accordingly, Drs Kaufman and Geiger have a proprietary interest. Alcon Laboratories, Inc, Fort Worth, Tex has paid a fee to University of Wisconsin and Weizmann Institute of Science for an option to license this technology and has provided some financial support in this general area. Dr Kaufman has served as a paid consultant on unrelated issues for Alcon Laboratories and several other pharmaceutical corporations.

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