title: Ketorolac eye drops reduce inflammation and delay re-epithelization in response to corneal alkali burn in rabbits, without affecting iNOS or MMP-9.
abstract: OBJECTIVE
  To assess the effects of 0.5% ketorolac tromethamine without preservatives on the expression of iNOS and MMP-9 in alkali burn ulcers.
  
  
  METHODS
  Twelve eyes of 120-day-old male rabbits were treated (TG) every 6 h with 0.5% ketorolac tromethamine and 12 other eyes were treated with saline solution (CG), immediately after the occurrence of ulcers by 1 M sodium hydroxide (NaOH). Re-epithelialization was monitored using fluorescein every 6 h. After 24 h, six corneas (n=6) of each group were collected (M1). The others (n=6) were collected after reepithelialization (M2). At both moments, the inflammatory infiltrate and the conditions of the newly formed epithelium were histologically analyzed. iNOS and MMP-9 were evaluated by immunohistochemistry.
  
  
  RESULTS
  Mean epithelialization time in TG was 55 ± 0.84 h. In CG, it was 44 ± 1.06 h (p=0.001). At M1, corneas of TG had lower inflammatory exudation compared with (p <0.001). At M2, TG revealed discrete inflammatory exudation (p>0.05) and lower numbers of epithelial layers compared with CG. The mean iNOS in stromal cells did not differ in TG over both moments compared with CG (p>0.05) At M2, the central corneal region expressed more iNOS in both groups compared with the peripheral region. No significant differences were observed in iNOS scores of epithelial immunostaining between the groups and across M1 and M2 (p=0.69). Epithelial immunostaining scores for MMP-9 did not differ in TG compared with CG (p=0.69). The average immunostaining score of MMP-9 in stromal cells showed no differences between groups or moments. There was no correlation between immunostaining of iNOS and MMP-9 or between the amount of inflammatory cells and immunostaining of iNOS.
  
  
  CONCLUSIONS
  Use of 0.5% keratolac tromethamine reduced inflammation and delayed reepithelialization in a cornea alkali burn model without impacting the expression of iNOS or MMP-9.
authors.affiliation: Department of Medicine and Surgery, College of Agricultural and Veterinarian Sciences, University of São Paulo, Jaboticabal, SP, Brazil.
authors.forename: Tiago Barbalho
authors.initials: TB
authors.lastname: Lima
authors.affiliation: Department of Veterinary Clinical Medicine, College of Veterinary and Agricultural Sciences, Federal University of Mato Grosso, Cuiabá, MT, Brazil.
authors.forename: Alexandre Pinto
authors.initials: AP
authors.lastname: Ribeiro
authors.affiliation: Department of Medicine and Surgery, College of Agricultural and Veterinarian Sciences, University of São Paulo, Jaboticabal, SP, Brazil.
authors.forename: Luciano Fernandes da
authors.initials: LF
authors.lastname: Conceição
authors.affiliation: Department of Veterinary Pathology, College of Agricultural and Veterinarian Sciences, University of São Paulo, Jaboticabal, SP, Brazil.
authors.forename: Marcio
authors.initials: M
authors.lastname: Bandarra
authors.affiliation: Department of Veterinary Pathology, College of Agricultural and Veterinarian Sciences, University of São Paulo, Jaboticabal, SP, Brazil.
authors.forename: Wilson Gomez
authors.initials: WG
authors.lastname: Manrique
authors.affiliation: Department of Medicine and Surgery, College of Agricultural and Veterinarian Sciences, University of São Paulo, Jaboticabal, SP, Brazil.
authors.forename: José Luiz
authors.initials: JL
authors.lastname: Laus
mesh_terms: D000468:Alkalies; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D002057:Burns, Chemical / Q000188:drug therapy; D003315:Cornea / Q000187:drug effects / Q000473:pathology; D003320:Corneal Ulcer / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D005126:Eye Burns / Q000139:chemically induced / Q000188:drug therapy; D007150:Immunohistochemistry; D020911:Ketorolac Tromethamine / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects*; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects*; D009883:Ophthalmic Solutions / Q000494:pharmacology / Q000627:therapeutic use*; D011817:Rabbits; D062326:Re-Epithelialization / Q000187:drug effects*; D015203:Reproducibility of Results; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000468:Alkalies; D000894:Anti-Inflammatory Agents, Non-Steroidal; D009883:Ophthalmic Solutions; D020911:Ketorolac Tromethamine; D052247:Nitric Oxide Synthase Type II; D020780:Matrix Metalloproteinase 9