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Topical application of AMA0076, a locally acting rho kinase (ROCK) inhibitor, results in a robust IOP control in a hypertensive rabbit model
Author(s) -
VAN DE VELDE S,
VAN BERGEN T,
VANDEWALLE E,
SIJNAVE D,
HOLLANDERS K,
LEYSEN D,
MOONS L,
STALMANS I
Publication year - 2011
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2011.3323.x
Subject(s) - latanoprost , bimatoprost , rho kinase inhibitor , medicine , prostaglandin , ophthalmology , intraocular pressure , ocular hypertension , pharmacology , rho associated protein kinase , aqueous humor , kinase , chemistry , biochemistry
Purpose To elucidate the IOP lowering effect of the local ROCK inhibitor, AMA0076, in the rabbit eye. Methods An ocular hypertensive rabbit model, based on the intracameral injection of visco‐elastic material, has been developed to determine the IOP lowering effect of compounds acting to improve aqueous humor outflow. Using this model, the IOP lowering effect of AMA0076 was tested and compared to Y‐39983, Latanoprost and Bimatoprost (5 rabbits/compound). Results Topical administration (TID) of AMA0076 prevented the IOP rise induced by the injection of visco‐elastics in a dose dependent manner (overall P<0.0001). Treatment with AMA0076 0.3% completely prevented the rise in IOP (overall P<0.0001). Administration of Y‐39983 0.3% significantly reduced (but did not completely abolish) IOP rise in the hypertensive model compared to the control eye (overall P<0.0001). A more subtle IOP decrease was also observed in the control eye with this non‐local ROCK inhibitor, presumably due to the systemic absorption of Y‐39983. AMA0076 was significantly more potent in blocking the IOP elevation in the hypertensive model compared to Latanoprost and Bimatoprost (respectively overall P=0.0004; P=0.0003). Conclusion The local ROCK inhibitor AMA0076 lowers IOP in an efficient manner in an acute rabbit model for ocular hypertension, with a potency exceeding that of the non‐local ROCK inhibitor Y‐39983, as well as the prostaglandin analogues Latanoprost and Bimatoprost. In summary, the present data indicate that this new class of ROCK inhibitors has potential therapeutic value for the treatment of glaucoma through a novel IOP lowering strategy.