H-7 increases trabecular facility and facility after ciliary muscle disinsertion in monkeys

Area of Science:

• Ophthalmology
• Pharmacology
• Physiology

Background:

• Glaucoma is a leading cause of irreversible blindness worldwide.
• Understanding the regulation of aqueous humor dynamics is crucial for developing effective glaucoma treatments.
• The serine-threonine kinase inhibitor H-7 has shown potential in modulating ocular outflow pathways.

Purpose of the Study:

• To investigate the impact of H-7 on total and trabecular outflow facility in primate eyes.
• To elucidate the role of the ciliary muscle (CM) in H-7's effect on ocular outflow.
• To determine if H-7 acts directly on the trabecular meshwork.

Main Methods:

• Total outflow facility was measured using two-level constant pressure perfusion of the anterior chamber in monkey eyes.
• Trabecular outflow facility was assessed by measuring the blood accumulation of radioiodinated albumin infused into the anterior chamber at different intraocular pressures.
• H-7 was administered both intracameral and topically, followed by anterior chamber exchange and infusion.

Main Results:

• Intracameral H-7 administration doubled outflow facility in iridectomized + CM-disinserted monkey eyes and iridectomized-only eyes.
• Topical H-7 application, followed by intracameral infusion, significantly increased trabecular and total outflow facility by 135% and 105%, respectively.
• These enhancements in outflow facility were statistically significant compared to vehicle-treated control eyes.

Conclusions:

• H-7 effectively increases trabecular outflow facility in monkeys.
• The mechanism of H-7 action appears to be independent of the ciliary muscle.
• These findings suggest that H-7 may act directly on the trabecular meshwork to improve aqueous humor drainage.