title: Carboxymethyl cellulose stimulates rabbit corneal epithelial wound healing.
abstract: OBJECTIVE
  Previously, we reported carboxymethyl cellulose (CMC) binding to human corneal epithelial cells and promoting corneal epithelial wound closure in vitro. Using an animal model, the efficacy of CMC in promoting corneal wound healing was examined.
  
  
  METHODS
  Following corneal epithelial wounding of NZ white rabbits, CMC (0.2% or 1.0%) or control vehicle (PBS) was administered topically (4 times daily for 3 days) to wounded and unwounded eyes with or without contact lens wear. Wound healing in response to the treatments was measured as percentage reduction of fluorescein-stained wound area 0 to 72 hr post-wounding. Corneas were examined histologically and expression of zonula occludens-1 (ZO-1) tight-junction was detected by immunohistochemistry.
  
  
  RESULTS
  Percentage wound reduction in CMC-treated groups was significantly greater than controls (p < 0.05) at 24 and 32 hr. Complete wound closure was observed by 48 hr in 100% of CMC-treated eyes compared to 45% of vehicle-treated eyes. CMC also promoted wound closure dose-dependently. Epithelial cells formed an intact layer following CMC-treatment whereas vehicle-treated cells were less ordered. Strong ZO-1 expression in corneal epithelia of CMC-treated eyes was observed at 72 hr. Contact lens wear appeared to delay wound closure compared to without lens wear during CMC-treatment (p = 0.001).
  
  
  CONCLUSIONS
  CMC promoted dose-dependent corneal epithelial wound healing. CMC stimulated ZO-1 expression, indicating accelerated corneal epithelial resistance barrier regeneration.
authors.affiliation: Institute for Eye Research, Sydney, New South Wales, Australia. q.garrett@ier.org.au
authors.forename: Qian
authors.initials: Q
authors.lastname: Garrett
authors.forename: Shunjiang
authors.initials: S
authors.lastname: Xu
authors.forename: Peter A
authors.initials: PA
authors.lastname: Simmons
authors.forename: Joseph
authors.initials: J
authors.lastname: Vehige
authors.forename: Ruo Zhong
authors.initials: RZ
authors.lastname: Xie
authors.forename: Ajay
authors.initials: A
authors.lastname: Kumar
authors.forename: Judith L
authors.initials: JL
authors.lastname: Flanagan
authors.forename: Zhenjun
authors.initials: Z
authors.lastname: Zhao
authors.forename: Mark D P
authors.initials: MD
authors.lastname: Willcox
mesh_terms: D000287:Administration, Topical; D000818:Animals; D002266:Carboxymethylcellulose Sodium / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D019573:Epithelium, Corneal / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D005131:Eye Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015590:Fluorophotometry; D007124:Immunoenzyme Techniques; D008565:Membrane Proteins / Q000378:metabolism; D009883:Ophthalmic Solutions / Q000008:administration & dosage / Q000494:pharmacology*; D010750:Phosphoproteins / Q000378:metabolism; D011817:Rabbits; D019108:Tight Junctions / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*; D062826:Zonula Occludens-1 Protein
chemical_list: D008565:Membrane Proteins; D009883:Ophthalmic Solutions; D010750:Phosphoproteins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D002266:Carboxymethylcellulose Sodium