title: Fasudil hydrochloride, a potent ROCK inhibitor, inhibits corneal neovascularization after alkali burns in mice.
abstract: OBJECTIVE
  To investigate the effects and mechanisms of fasudil hydrochloride (fasudil) on and in alkali burn-induced corneal neovascularization (CNV) in mice.
  
  
  METHODS
  To observe the effect of fasudil, mice with alkali-burned corneas were treated with either fasudil eye drops or phosphate-buffered saline (PBS) four times per day for 14 consecutive days. After injury, CNV and corneal epithelial defects were measured. The production of reactive oxygen species (ROS) and heme oxygenase-1(HO-1) was measured. The infiltration of polymorphonuclear neutrophils (PMNs) and the mRNA expressions of CNV-related genes were analyzed on day 14.
  
  
  RESULTS
  The incidence of CNV was significantly lower after treatment with 100 μM and 300 μM fasudil than with PBS, especially with 100 μM fasudil. Meanwhile, the incidences of corneal epithelial defects was lower (n=15, all p<0.01). After treatment with 100 μM fasudil, the intensity of DHE ﬂuorescence was reduced in the corneal epithelium and stroma than with PBS treatment (n=5, all p<0.01), and the number of filtrated PMNs decreased. There were significant differences between the expressions of VEGF, TNF-a, MMP-8, and MMP-9 in the 100 μM fasudil group and the PBS group (n=8, all p<0.05). The production of HO-1 protein in the 100 μM fasudil group was 1.52±0.34 times more than in the PBS group (n=5 sample, p<0.05).
  
  
  CONCLUSIONS
  100 μM fasudil eye drops administered four times daily can significantly inhibit alkali burn-induced CNV and promote the healing of corneal epithelial defects in mice. These effects are attributed to a decrease in inflammatory cell infiltration, reduction of ROS, and upregulation of HO-1 protein after fasudil treatment.
authors.affiliation: Zhongshan Ophthalmic Center of Sun Yat-sen University, The State Key Laboratory of Ophthalmology,Guangzhou, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zeng
authors.affiliation: Department of Pharmacology & Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Rong-biao
authors.initials: RB
authors.lastname: Pi
authors.affiliation: Department of Ophthalmology, No.181 Hospital of PLA, Guangxi, Guilin, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Zhongshan Ophthalmic Center of Sun Yat-sen University, The State Key Laboratory of Ophthalmology,Guangzhou, China.
authors.forename: Rong-xin
authors.initials: RX
authors.lastname: Chen
authors.affiliation: Zhongshan Ophthalmic Center of Sun Yat-sen University, The State Key Laboratory of Ophthalmology,Guangzhou, China.
authors.forename: Li-mian
authors.initials: LM
authors.lastname: Lin
authors.affiliation: Hainan Eye Hospital of Zhongshan Ophthalmic Center, Haikou, Hainan Province, China.
authors.forename: Hong
authors.initials: H
authors.lastname: He
authors.affiliation: Zhongshan Ophthalmic Center of Sun Yat-sen University, The State Key Laboratory of Ophthalmology,Guangzhou, China.
authors.forename: Shi-you
authors.initials: SY
authors.lastname: Zhou
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000468:Alkalies / Q000633:toxicity; D000818:Animals; D002057:Burns, Chemical / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D016510:Corneal Neovascularization / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D005126:Eye Burns / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D005260:Female; D051547:Heme Oxygenase-1 / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000468:Alkalies; D008565:Membrane Proteins; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D054460:rho-Associated Kinases; C049347:fasudil