Journal
CURRENT EYE RESEARCH
Volume 22, Issue 2, Pages 109-120Publisher
SWETS ZEITLINGER PUBLISHERS
DOI: 10.1076/ceyr.22.2.109.5529
Keywords
aqueous humor flow; ciliary epithelium; corneal endothelium; cynomolgus monkey; fluorophotometry; H-7
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Funding
- NATIONAL EYE INSTITUTE [R01EY002698] Funding Source: NIH RePORTER
- NEI NIH HHS [EY02698] Funding Source: Medline
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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.
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