Effects of a Ripasudil–Brimonidine Fixed-Dose Combination on Intraocular Pressure, Outflow Facility, and Episcleral Venous Pressure in Mouse Eyes

Abstract

Abstract Ripasudil–brimonidine fixed-dose combination (K-232) simultaneously targets three different intraocular pressure (IOP) lowering mechanisms, increasing trabecular meshwork outflow and uveoscleral outflow, and reducing aqueous humor production Vascularly, ripasudil induces transient vasodilation, brimonidine transient vasoconstriction. Investigating effects on IOP, aqueous dynamics, and EVP in mice eyes by microneedle and constant-pressure perfusion methods, and on cytoskeletal and fibrotic proteins changes in HTM cells by a gel contraction assay and immunocytochemistry. Ripasudil, K-232, and brimonidine droplets significantly reduced IOP at 30 min, with K-232 sustaining the effect at 60 min. For EVP, only K-232 exhibited prolonged reduction. In vitro, ripasudil inhibited gel contractility and TGFβ2-induced fibrotic changes; brimonidine had limited effects. K-232 significantly lowered IOPs in mice by combining the effects of ripasudil and brimonidine. Brimonidine alone also showed IOP reductions with enhanced outflow facility, possibly due to the EVP reduction; however, the drug did not interfere with the effects of ripasudil on the trabecular meshwork outflow. K-232 and ripasudil alone both significantly lowered the EVP and enhanced outflow facility, demonstrating that K-232 efficiently reduces IOPs.