Effects of topical H-7 on outflow facility, intraocular pressure, and corneal thickness in monkeys.
OBJECTIVE
To determine if low concentrations of H-7 (1-[5-isoquinoline sulfonyl]-2-methyl piperazine) topically applied to the eye increases outflow facility and decreases intraocular pressure (IOP) without affecting the cornea in monkeys, and to evaluate if the effect of H-7 on IOP is pressure dependent.


METHODS
Single or multiple doses of 5% H-7 or vehicle (20 micro L) were administered topically to opposite eyes of normal monkeys. A single dose of 2% H-7 or vehicle (50 micro L) was administered to the glaucomatous eye of monkeys with laser-induced unilateral glaucoma, with vehicle on day 1 and H-7 on day 2.


RESULTS
In normotensive eyes, 1 dose of 5% H-7 maximally decreased IOP by a mean +/- SEM of 2.5 +/- 1.0 mm Hg (-16.7% +/- 5.5%) at 3 hours. Higher baseline IOP and repeated dosing were associated with greater IOP reduction. Outflow facility was increased, but central corneal thickness was not affected. In glaucomatous eyes, 1 dose of 2% H-7 maximally decreased IOP by a mean +/- SEM of 5.8 +/- 0.6 mm Hg (-16.9% +/- 1.6%) at 2 hours.


CONCLUSIONS
Five percent H-7 increases outflow facility and decreases IOP, but does not affect corneal thickness. Multiple doses of H-7 induce greater reduction of IOP than a single dose. The effect of H-7 on IOP may be pressure dependent. Clinical Relevance Multiple topical treatments with low doses of H-7 or analogues may substantially reduce outflow resistance in the hypertensive eye without meaningfully affecting the cornea.
Tian
Baohe
B
Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison Medical School, 53792-3284, USA.
Wang
Rong-Fang
RF
Podos
Steven M
SM
Kaufman
Paul L
PL
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000008:administration & dosage*; D000287:Administration, Topical; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism*; D003315:Cornea / Q000187:drug effects*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D005260:Female; D005901:Glaucoma / Q000188:drug therapy* / Q000378:metabolism; D007429:Intraocular Pressure / Q000187:drug effects*; D017075:Laser Coagulation; D008252:Macaca fascicularis; D008297:Male; D009883:Ophthalmic Solutions; D014129:Trabecular Meshwork / Q000187:drug effects* / Q000601:surgery
D004791:Enzyme Inhibitors; D009883:Ophthalmic Solutions; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine