Document Detail

The ROCK inhibitor eye drop accelerates corneal endothelium wound healing.
MedLine Citation:
PMID:  23462749     Owner:  NLM     Status:  MEDLINE    
PURPOSE: To evaluate the effect of Rho kinase (ROCK)-inhibitor eye drops on a corneal endothelial dysfunction primate model and human clinical case series of corneal endothelial dysfunction.
METHODS: As a corneal-endothelial partially injured model, the corneal endothelium of seven cynomolgus monkeys was damaged by transcorneal freezing; 10 mm of rock inhibitor Y-27632 was then applied topically 6 times daily. The phenotype of the reconstructed corneal endothelium was evaluated by immunohistochemical analysis and noncontact specular microscopy. For clinical study, the effect of Y-27632 eye drops after transcorneal freezing was evaluated in eight corneal endothelial dysfunction patients: four central corneal edema patients and four diffuse corneal edema patients.
RESULTS: Slit-lamp microscopy revealed that both Y-27632-treated and -nontreated corneas became hazy after transcorneal freezing, and then recovered their transparency within 4 weeks. ROCK inhibitor Y-27632 promoted recovery of corneal endothelial cell density and wound healing in terms of both morphology and function. The percentage of ZO-1 and Na(+)/K(+)-ATPase positive cells in the regenerated area in the Y-27632 group was significantly higher than in the controls. Noncontact specular microscopy revealed that corneal endothelial cell density was significantly higher in the Y-27632 group compared with the controls at 4 weeks; cell density reached approximately 3000 cells/mm(2), as opposed to 1500 cells/mm(2) in the control group. In addition to the animal study findings, the clinical study findings showed that Y-27632 eye drops effectively improved corneal edema of corneal endothelial dysfunction patients with central edema.
CONCLUSIONS: These findings show that rock inhibitor Y-27632 eye drops promote corneal endothelial wound healing in a primate animal model and suggest the possibility of Y-27632 as a novel therapeutic modality for certain forms of corneal endothelial dysfunction. ( number, UMIN000003625.).
Naoki Okumura; Noriko Koizumi; Eunduck P Kay; Morio Ueno; Yuji Sakamoto; Shinichiro Nakamura; Junji Hamuro; Shigeru Kinoshita
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-04-03
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  54     ISSN:  1552-5783     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-04     Completed Date:  2013-05-29     Revised Date:  2013-10-07    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2493-502     Citation Subset:  IM    
Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
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MeSH Terms
Administration, Topical
Amides / therapeutic use*
Cell Count
Corneal Edema / drug therapy*,  metabolism,  pathology
Corneal Endothelial Cell Loss / physiopathology
Disease Models, Animal*
Endothelium, Corneal / enzymology,  injuries,  ultrastructure
Enzyme Inhibitors / therapeutic use*
Eye Injuries / drug therapy,  metabolism,  pathology
Macaca fascicularis
Middle Aged
Ophthalmic Solutions
Pyridines / therapeutic use*
Sodium-Potassium-Exchanging ATPase / metabolism
Wound Healing / drug effects*
Wounds, Nonpenetrating / drug therapy*,  metabolism,  pathology
Zonula Occludens-1 Protein / metabolism
rho-Associated Kinases / antagonists & inhibitors*
Reg. No./Substance:
0/Amides; 0/Enzyme Inhibitors; 0/Ophthalmic Solutions; 0/Pyridines; 0/Zonula Occludens-1 Protein; 138381-45-0/Y 27632; EC Kinases; EC ATPase
Comment In:
Invest Ophthalmol Vis Sci. 2013;54(8):5594-5   [PMID:  23960040 ]
Invest Ophthalmol Vis Sci. 2013 Jul;54(7):4971-3   [PMID:  23883789 ]

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