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

Kaufman Lab // Publications // Feb 01 2001

PubMed ID: 11402388

Author(s): Tian B, Sabanay I, Peterson JA, Hubbard WC, Geiger B, Kaufman PL. Acute effects of H-7 on ciliary epithelium and corneal endothelium in monkey eyes. Curr Eye Res. 2001 Feb;22(2):109-20. PMID 11402388

Journal: Current Eye Research, Volume 22, Issue 2, Feb 2001

PURPOSE Topical or intracameral administration of H-7 doubles outflow facility and reduces intraocular pressure in cynomolgus monkeys, by relaxing and expanding the trabecular meshwork (TM) and Schlemm’s canal (SC). Since H-7 may have anti-glaucoma potential, we determined its effects on the corneal endothelium and ciliary epithelium for safety considerations.

METHODS Following topical H-7, aqueous humor flow (AHF), corneal endothelial transfer coefficient (k(a)) and anterior chamber (AC) entry of i.v. fluorescein 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 pachymetry and specular microscopy respectively. Following intracameral H-7, specular and/or light and electron microscopy of the corneal endothelium or ciliary epithelium were performed.

RESULTS Following unilateral topical H-7: (1) AHF and k(a) were essentially unchanged at 0.5–3.0, 3.5–6.0, and 0.5–6.0 hr, with an insignificant increase 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. fluorescein into aqueous or cornea was modestly and transiently increased; (4) the central cornea thickened significantly at 1–2.5 hr, gradually returning to baseline 2.5 hr after H-7, while peripheral corneal thickness was less affected; (5) corneal endothelial cell borders became indistinct by 1 hr, but cell 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. Following intracameral H-7, no significant changes were observed in corneal endothelial cell density or morphology by specular microscopy, nor in corneal endothelial or ciliary epithelial morphology by light and electron microscopy.

CONCLUSIONS A facility-effective intracameral dose of H-7 had no discernible structural effect on the corneal endothelium or ciliary epithelium. It is 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.