title: Matrix-Based Regenerating Agent for Corneal Wound Healing After Collagen Cross-Linking.
abstract: OBJECTIVE
  Corneal collagen cross-linking (CXL) is associated with massive cellular damage, the long-term clinical consequences of which have still to be elucidated. In this study, we seek to determine whether matrix-based regenerating agent (RGTA) therapy has a positive influence on stromal regeneration after CXL.
  
  
  METHODS
  Twelve New Zealand white rabbits were randomly divided into 2 groups of 6. CXL of the right cornea was performed in both groups, followed by topical corneal application of one drop of vehicle or one drop of RGTA. In vivo confocal laser-scanning microscopy was used to monitor corneal changes over time. At the end of the experiment, 2 weeks postoperatively, the corneas were excised and processed for histology.
  
  
  RESULTS
  Epithelial healing was noted in both groups 3 days after CXL. One week after treatment, in vivo confocal laser-scanning microscopy in both groups revealed a significantly thicker acellular stromal zone in the vehicle group compared with the RGTA group (P = 0.0165). This difference persisted up to 2 weeks postoperatively, when acellular zone thickness was 96 ± 10 µm in the RGTA group and 146 ± 34 µm in the vehicle group (P = 0.0058). These findings were confirmed by histology, which also revealed earlier cell repopulation in the RGTA group.
  
  
  CONCLUSIONS
  The anterior stroma of cross-linked corneas exhibited cell loss after CXL. Cell repopulation in the anterior corneal stroma occurred earlier when CXL was followed by topical RGTA treatment. Further studies are required to examine the impact of this ophthalmic RGTA on corneal nerve regeneration after CXL.
authors.affiliation: *Institute for Biomedical Engineering, Rostock University Medical Center, Rostock, Germany;†Department of Ophthalmology, Rostock University Medical Center, Rostock, Germany; and‡Laboratoires Théa, Clermont-Ferrand, France.
authors.forename: Marina
authors.initials: M
authors.lastname: Hovakimyan
authors.forename: Oliver
authors.initials: O
authors.lastname: Stachs
authors.forename: Olmiere
authors.initials: O
authors.lastname: Céline
authors.forename: Rudolf F
authors.initials: RF
authors.lastname: Guthoff
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism*; D003315:Cornea / Q000294:innervation; D060527:Corneal Keratocytes / Q000502:physiology; D003319:Corneal Stroma / Q000378:metabolism*; D003432:Cross-Linking Reagents; D019573:Epithelium, Corneal / Q000502:physiology; D006025:Glycosaminoglycans / Q000627:therapeutic use*; D018613:Microscopy, Confocal; D009412:Nerve Fibers / Q000473:pathology; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011184:Postoperative Period; D011817:Rabbits; D062326:Re-Epithelialization; D012256:Riboflavin / Q000627:therapeutic use; D014276:Trigeminal Nerve / Q000473:pathology; D014466:Ultraviolet Rays; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D003432:Cross-Linking Reagents; D006025:Glycosaminoglycans; C533322:OTR4120; D017319:Photosensitizing Agents; D003094:Collagen; D012256:Riboflavin