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The ROCK inhibitor eye drop accelerates corneal endothelium wound healing.

AbstractPURPOSE:
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. (http://www.umin.ac.jp/ctr/ number, UMIN000003625.).
AuthorsNaoki Okumura, Noriko Koizumi, Eunduck P Kay, Morio Ueno, Yuji Sakamoto, Shinichiro Nakamura, Junji Hamuro, Shigeru Kinoshita
JournalInvestigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 54 Issue 4 Pg. 2493-502 (Apr 2013) ISSN: 1552-5783 [Electronic] United States
PMID23462749 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Amides
  • Enzyme Inhibitors
  • Ophthalmic Solutions
  • Pyridines
  • Zonula Occludens-1 Protein
  • Y 27632
  • rho-Associated Kinases
  • Sodium-Potassium-Exchanging ATPase
Topics
  • Administration, Topical
  • Aged
  • Amides (therapeutic use)
  • Animals
  • 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)
  • Female
  • Humans
  • Macaca fascicularis
  • Male
  • 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)

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