Morphological and hydrodynamic correlations with increasing outflow facility by rho-kinase inhibitor Y-27632.
Abstract Rho-kinase inhibitors affect actomyosin cytoskeletal networks and have been shown to significantly increase outflow facility and lower intraocular pressure in various animal models and human eyes. This article summarizes common morphological changes in the trabecular meshwork induced by Rho-kinase inhibitors and specifically compares the morphological and hydrodynamic correlations with increased outflow facility by Rho-kinase inhibitor, Y-27632, in bovine, monkey, and human eyes under similar experimental conditions. Interspecies comparison has shown that morphological changes in the juxtacanalicular connective tissue (JCT) of these 3 species were different. However, these different morphological changes in the JCT, no matter if it's separation between the JCT and inner wall in bovine eyes, or separation between the JCT cells or between the JCT cells and their matrix in monkey eyes, or even no separation between the inner wall and the JCT but a more subtle expansion of the JCT in human eyes, appear to correlate with the increased percent change of outflow facility. More importantly, these different morphological changes all resulted in an increase in effective filtration area, which was positively correlated with increased outflow facility in all 3 species. These results suggest a link among changes in outflow facility, tissue architecture, and aqueous outflow pattern. Y-27632 increases outflow facility by redistributing aqueous outflow through a looser and larger area in the JCT.
1 Department of Ophthalmology, Boston University School of Medicine , Boston, Massachusetts.
Haiyan
H
Gong
Chen-Yuan Charlie
CY
Yang
D000577:Amides / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001082:Aqueous Humor / Q000187:drug effects / Q000378:metabolism; D002417:Cattle; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000882:Haplorhini; D006801:Humans; D057446:Hydrodynamics; D007429:Intraocular Pressure / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology*; D013045:Species Specificity; D014129:Trabecular Meshwork / Q000187:drug effects / Q000378:metabolism; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
D000577:Amides; D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D011725:Pyridines; C108830:Y 27632; D054460:rho-Associated Kinases