title: The ROCK inhibitor eye drop accelerates corneal endothelium wound healing.
abstract: OBJECTIVE
  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.).
authors: Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors: Naoki
authors: N
authors: Okumura
authors: Noriko
authors: N
authors: Koizumi
authors: Eunduck P
authors: EP
authors: Kay
authors: Morio
authors: M
authors: Ueno
authors: Yuji
authors: Y
authors: Sakamoto
authors: Shinichiro
authors: S
authors: Nakamura
authors: Junji
authors: J
authors: Hamuro
authors: Shigeru
authors: S
authors: Kinoshita
mesh_terms: D000287:Administration, Topical; D000368:Aged; D000577:Amides / Q000627:therapeutic use*; D000818:Animals; D002452:Cell Count; D015715:Corneal Edema / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D055954:Corneal Endothelial Cell Loss / Q000503:physiopathology; D004195:Disease Models, Animal; D004728:Endothelium, Corneal / Q000201:enzymology / Q000293:injuries / Q000648:ultrastructure; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005131:Eye Injuries / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008252:Macaca fascicularis; D008297:Male; D008875:Middle Aged; D009883:Ophthalmic Solutions; D011725:Pyridines / Q000627:therapeutic use*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*; D014949:Wounds, Nonpenetrating / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D062826:Zonula Occludens-1 Protein / Q000378:metabolism; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D009883:Ophthalmic Solutions; D011725:Pyridines; D062826:Zonula Occludens-1 Protein; C108830:Y 27632; D054460:rho-Associated Kinases; D000254:Sodium-Potassium-Exchanging ATPase