title: RGTA in corneal wound healing after transepithelial laser ablation in a rabbit model: a randomized, blinded, placebo-controlled study.
abstract: OBJECTIVE
  To evaluate the efficacy of the agent RGTA for epithelial, stromal and nerve regeneration after laser-induced corneal wounding in rabbits.
  
  
  METHODS
  After excimer laser wounding of the anterior cornea in 25 New Zealand white rabbits, topical RGTA or placebo was applied in a randomized, masked manner. Fluorescein epithelial staining was performed on the first 5 postoperative days. In vivo confocal microscopy of corneal subbasal nerves and stroma was performed preoperatively and on week 2, 4, 8 and 16. At 16 weeks, corneas were stained for beta-III tubulin expression.
  
  
  RESULTS
  Postoperatively, all epithelia had closed by at least 90% after the third postoperative day. No significant difference in epithelial wound size was found between RGTA and placebo-treated groups, and RGTA did not hinder fluorescein binding. After epithelial wound closure, corneas remained transparent to 16 weeks. By confocal microscopy, subclinical stromal haze was significantly deeper in placebo-treated eyes (mean depth 60 μm) relative to RGTA group (52 μm), p = 0.02. Regenerating beta-III tubulin-positive subbasal nerves were observed in all corneas, but partial masking by haze rendered quantitative analysis unreliable.
  
  
  CONCLUSIONS
  RGTA restored stromal microarchitecture and reduced subclinical haze relative to placebo. The mild epithelial wound quickly healed regardless of treatment suggesting an optimal natural healing process in freshly wounded healthy corneas, and indicating that RGTA may be more suitable for healing of chronic or more aggressive wounds. Limitations of the rabbit model for nerve quantification in the presence of haze should also be recognized.
authors.affiliation: Division of Ophthalmology, Institute for Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Xeroudaki
authors.affiliation: Division of Ophthalmology, Institute for Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Peebo
authors.affiliation: Division of Ophthalmology, Institute for Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Germundsson
authors.affiliation: Division of Ophthalmology, Institute for Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Fagerholm
authors.affiliation: Division of Ophthalmology, Institute for Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden. neil.lagali@liu.se.
authors.forename: Neil
authors.initials: N
authors.lastname: Lagali
mesh_terms: D000818:Animals; D003315:Cornea / Q000294:innervation / Q000601:surgery*; D003319:Corneal Stroma / Q000502:physiology; D019573:Epithelium, Corneal / Q000502:physiology; D015590:Fluorophotometry; D006025:Glycosaminoglycans / Q000627:therapeutic use*; D054018:Lasers, Excimer / Q000627:therapeutic use*; D018613:Microscopy, Confocal; D023421:Models, Animal; D009416:Nerve Regeneration / Q000187:drug effects*; D018903:Photorefractive Keratectomy; D011817:Rabbits; D014276:Trigeminal Nerve / Q000502:physiology*; D014404:Tubulin / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D006025:Glycosaminoglycans; C533322:OTR4120; D014404:Tubulin
keywords: 
  RGTA
  ; Cacicol; cornea; epithelium; excimer laser; regeneration; subbasal nerves