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Effects of Rho Kinase Inhibitors on Intraocular Pressure and Aqueous Humor Dynamics in Nonhuman Primates and Rabbits
- Source :
- Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics. 32(6)
- Publication Year :
- 2016
-
Abstract
- This study examines the effects of 2 Rho kinase inhibitors on intraocular pressure (IOP) and aqueous humor dynamics.IOPs of New Zealand albino rabbits with ocular normotension and cynomolgus macaques (nonhuman primate, NHP) with chronic unilateral laser-induced glaucoma were measured at baseline and periodically after a 9 a.m. dose of H-1152, Y-27632, or vehicle. In a separate group of NHPs, aqueous flow, outflow facility, uveoscleral outflow, and IOP were determined after treatment with Y-27632 or vehicle control.Decreases in IOP were found in rabbits (n = 5) at 6 h after one dose of 2% Y-27632 (29%, P = 0.0002) or 1% H-1152 (35%, P = 0.0001), and in hypertensive eyes of NHPs (n = 7-9) at 3 h after one dose of 2% Y-27632 (35%, P = 0.005) or 1% H-1152 (51%, P = 0.0003). With 2 doses of 1% Y-27632 or vehicle in NHP hypertensive eyes (n = 12), significant drug effects were IOP reduction of 28% (P = 0.05) at 2.5 h after the second dose and increases in aqueous flow (36%; P = 0.013), uveoscleral outflow (59%, P = 0.008), and outflow facility (40%; P = 0.01). In normotensive eyes of the same animals, aqueous flow increased by 21% (P = 0.03). No significant change was found in any of the other parameters.Y-27632 and H-1152 lower IOP in rabbits and hypertensive eyes of NHPs for at least 6 h after single doses. The Y-27632 effect on IOP in hypertensive NHP eyes is caused by increases in outflow facility and uveoscleral outflow. An increase in aqueous humor formation attenuates but does not prevent an IOP decrease.
- Subjects :
- 0301 basic medicine
Intraocular pressure
medicine.medical_specialty
genetic structures
New Zealand Albino
Uveoscleral outflow
Pyridines
Glaucoma
Aqueous humor
Corrections
Aqueous Humor
03 medical and health sciences
0302 clinical medicine
Ophthalmology
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
Medicine
Animals
Pharmacology (medical)
Rho-associated protein kinase
Protein Kinase Inhibitors
Intraocular Pressure
Pharmacology
rho-Associated Kinases
business.industry
Aqueous flow
medicine.disease
Amides
eye diseases
Nonhuman primate
Macaca fascicularis
030104 developmental biology
Anesthesia
030221 ophthalmology & optometry
sense organs
Rabbits
business
Subjects
Details
- ISSN :
- 15577732
- Volume :
- 32
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics
- Accession number :
- edsair.doi.dedup.....e5948d4c0e1d2860f7052e9b6a9a47bb