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Megumi Honjo, Hidenobu Tanihara, Masaru Inatani, Noriaki Kido, Tatsuya Sawamura, Beatrice Y. J. T. Yue, Shuh Narumiya, Yoshihito Honda; Effects of Rho-Associated Protein Kinase Inhibitor Y-27632 on Intraocular Pressure and Outflow Facility. Invest. Ophthalmol. Vis. Sci. 2001;42(1):137-144. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
purpose. To elucidate the roles of Rho-associated protein kinase (ROCK) in
regulating intraocular pressure (IOP) and outflow facility in the
methods. A specific ROCK inhibitor Y-27632 was used. The IOP, the outflow
facility, and the pupil diameter were determined before and after the
topical, intracameral, or intravitreal administration of Y-27632 in
rabbits. Western blot analysis was used to identify specific ROCK
isoform in human trabecular meshwork (TM) cells and bovine ciliary
muscle (CM) tissues. The cell morphology and distribution of actin
filaments and vinculin in TM cells were studied by cell biology
techniques. Carbachol (Cch)-induced contraction of isolated bovine CM
strips after administration of Y-27632 was measured in a perfusion
results. In rabbit eyes, administration of Y-27632 resulted in a significant
decrease in IOP in a dose-dependent manner. An increase of the outflow
facility and pupil size dilation was also observed in Y-27632–treated
eyes. Western blot analysis revealed the presence of p160ROCK in human
TM cells and bovine CM tissues. In cultured human TM cells, exposure to
Y-27632 caused retraction and rounding of cell bodies as well as
disruption of actin bundles and impairment of focal adhesion formation.
Y-27632 in addition inhibited Cch-induced contraction of isolated
bovine CM strips.
conclusions. Administration of Y-27632 caused a reduction in IOP and an increase in
the outflow facility. The in vitro experiments suggest that the
IOP-lowering effects of Y-27632 may be related to the altered cellular
behavior of TM cells and relaxation of CM contraction. These studies
suggest that ROCK inhibitors may have great potential to be developed
for treatment of glaucoma and other ocular
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