title: Recovery of corneal sensitivity, calcitonin gene-related peptide-positive nerves, and increased wound healing induced by pigment epithelial-derived factor plus docosahexaenoic acid after experimental surgery.
abstract: OBJECTIVE
  To assess function of regenerated corneal nerves in correlation with epithelial wound healing after experimental nerve damage in rabbits treated with pigment epithelial-derived factor (PEDF) plus docosahexaenoic acid (DHA).
  
  
  METHODS
  An 8-mm stromal dissection was performed in the right eyes of adult New Zealand rabbits. Treatment with PEDF+DHA was for 6 weeks. Corneal sensation was measured weekly by Cochet-Bonnet esthesiometer. After 8 weeks, immunofluorescence with βIII-tubulin, calcitonin gene-related peptide, and substance P antibodies was performed to quantify nerves. Also, rabbits were treated with PEDF+DHA for 4 weeks after lamellar keratectomy, followed by 8-mm epithelial debridement and epithelial defect assessment. One week after surgery, corneas were stained with anti-Ki67 antibody to assess cell proliferation.
  
  
  RESULTS
  Eight weeks after surgery, calcitonin gene-related peptide-positive nerve fibers in the PEDF+DHA group were similar to normal rabbit corneas but were decreased in the vehicle. Substance P was localized in the subepithelial plexus but appeared in epithelial cells after nerve injury regardless of treatment. Five weeks after surgery, an increase in corneal sensitivity occurred in the PEDF+DHA group and reached normal values by 8 weeks. Pigment epithelial-derived factor plus DHA increased epithelial wound healing after lamellar keratectomy. One week after epithelial injury, Ki67-positive cells increased in the limbal area.
  
  
  CONCLUSIONS
  Pigment epithelial-derived factor plus DHA promotes regeneration of calcitonin gene-related peptide-positive corneal nerves, accelerating wound healing and return of corneal sensitivity.
  
  
  CONCLUSIONS
  Pigment epithelial-derived factor plus DHA represents a new approach to regenerate nerves and a potential treatment for prevention of severe dry eye after surgery or diseases of the ocular surface.
authors.affiliation: Department of Ophthalmology, University of Illinois Medical Center, Chicago, USA.
authors.forename: M Soledad
authors.initials: MS
authors.lastname: Cortina
authors.forename: Jiucheng
authors.initials: J
authors.lastname: He
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Nicolas G
authors.initials: NG
authors.lastname: Bazan
authors.forename: Haydee E P
authors.initials: HE
authors.lastname: Bazan
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D003315:Cornea / Q000294:innervation / Q000502:physiology*; D003319:Corneal Stroma / Q000601:surgery*; D016039:Corneal Transplantation; D003646:Debridement; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D019573:Epithelium, Corneal / Q000378:metabolism / Q000601:surgery; D005136:Eye Proteins / Q000494:pharmacology*; D019084:Fluorescent Antibody Technique, Indirect; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D009882:Ophthalmic Nerve / Q000293:injuries / Q000378:metabolism*; D011817:Rabbits; D020127:Recovery of Function / Q000502:physiology; D015843:Serpins / Q000494:pharmacology*; D013373:Substance P / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D015740:Calcitonin Gene-Related Peptide; D004281:Docosahexaenoic Acids; D005136:Eye Proteins; D019394:Ki-67 Antigen; D009414:Nerve Growth Factors; D015843:Serpins; D013373:Substance P; D014404:Tubulin; D000099174:Pigment Epithelium-Derived Factor