Acute effects of H-7 on ciliary epithelium and corneal endothelium in monkey eyes

Purpose. Topical or intracameral administration of H-7 doubles outflow faci lity and reduces intraocular pressure in cynomolgus monkeys, by relaxing an d expanding the trabecular meshwork (TM) and Schlemm's canal (SC). Since H- 7 may have anti-glaucoma potential, we determined its effects on the cornea l endothelium and ciliary epithelium for safety considerations. Methods. Following topical H-7, aqueous humor flow (AHF), corneal endotheli al transfer coefficient (k(a)) and anterior chamber (AC) entry of i.v. fluo rescein were measured by fluorophotometry; AC aqueous protein concentration ([ Protein](AC)) was determined by Lowry assay; and corneal thickness and endothelial cell density and morphology were measured by ultrasonic pachyme try and specular microscopy respectively. Following intracameral H-7, specu lar and/or light and electron microscopy of the corneal endothelium or cili ary epithelium were performed. Results. Following unilateral topical H-7: (1) AHF and k(a) were essentiall y unchanged at 0.5-3.0, 3.5-6.0, and 0.5-6.0 hr, with an insignificant incr ease from 0.5-1.5 hr; (2) [Protein](AC) was insignificantly increased at 1- 1.5 hr but had returned to baseline by 2.5 hr; (3) entry of i.v. fluorescei n into aqueous or cornea was modestly and transiently increased; (4) the ce ntral cornea thickened significantly at 1-2.5 hr, gradually returning to ba seline 2.5 hr after H-7, while peripheral corneal thickness was less affect ed; (5) corneal endothelial cell borders became indistinct by 1 hr, but cel l morphology was recovering by 3-5 hr and had completely returned to normal by 24 hr; (6) corneal endothelial cell density was unchanged at 5-24 hr. F ollowing intracameral H-7, no significant changes were observed in corneal endothelial cell density or morphology by specular microscopy, nor in corne al endothelial or ciliary epithelial morphology by light and electron micro scopy. Conclusions. A facility-effective intracameral dose of H-7 had no discernib le structural effect on the corneal endothelium or ciliary epithelium. It i s not yet clear whether carefully chosen topical doses of H-7 or analogues can enhance outflow facility without meaningfully affecting the cornea and ciliary processes.