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

• Published in: Current eye research 2001-01, Vol.22 (2), p.109-120
• Main Authors: Tian, Baohe, Sabanay, Ilana, Peterson, Jennifer A., Hubbard, William C., Geiger, Benjamin, Kaufman, Paul L.
• Format: Article
• Language: English
• Subjects: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - administration & dosage; 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - pharmacology; Administration, Topical; Animals; Aqueous Humor - metabolism; Cell Count; Cell Size; Ciliary Body - drug effects; Ciliary Body - metabolism; Ciliary Body - ultrastructure; Drug Evaluation, Preclinical; Endothelium, Corneal - drug effects; Endothelium, Corneal - metabolism; Endothelium, Corneal - ultrastructure; Enzyme Inhibitors - administration & dosage; Enzyme Inhibitors - pharmacology; Eye Proteins - metabolism; Female; Fluorescein - metabolism; Fluorophotometry; Macaca fascicularis; Male; Pigment Epithelium of Eye - drug effects; Pigment Epithelium of Eye - metabolism; Pigment Epithelium of Eye - ultrastructure; Protein-Serine-Threonine Kinases - antagonists & inhibitors
• ISSN: 0271-3683; 1460-2202
• DOI: 10.1076/ceyr.22.2.109.5529

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.