title: The PEDF Neuroprotective Domain Plus DHA Induces Corneal Nerve Regeneration After Experimental Surgery.
abstract: OBJECTIVE
  To compare a 44-mer pigment epithelial-derived factor (PEDF) peptide with neurotrophic activity, and a 34-mer PEDF with antiangiogenic properties in association with docosahexaenoic acid (DHA) in corneal nerve regeneration after experimental surgery.
  
  
  METHODS
  A corneal stromal dissection was performed in rabbits. Treatment groups received topical 44-mer, 34-mer, or full PEDF plus DHA. Corneal sensitivity and Schirmer's test were performed weekly. Rabbits were euthanized at 2 and 4 days and 8 weeks. Two- and 4-day samples were stained for neutrophils and CD11b+ cells. Corneal nerves were stained with βIII tubulin and calcitonin gene-related peptide (CGRP) antibodies in specimens collected at 8 weeks. Subepithelial nerve plexus density was calculated. A PEDF-receptor (PEDF-R) was analyzed in rabbit corneal epithelial cells (RCEC) by Western blot and immunofluorescence.
  
  
  RESULTS
  Infiltration of CD11b+cells and neutrophils was reduced by treatment with 44-mer PEDF+DHA. A 3-fold increase in subepithelial corneal nerves and CGRP-positive nerves was found in the 44-mer PEDF+DHA-treated group compared with the 34-mer PEDF+DHA- and vehicle-treated groups. There was a 75% recovery of corneal sensitivity by week 7, and Schirmer's test reached control values in the 44-mer PEDF+DHA-treated corneas at 7 weeks. A PEDF-R protein with homology to calcium-independent phospholipase A2ς was expressed in RCEC.
  
  
  CONCLUSIONS
  The 44-mer PEDF+DHA, but not the 34-mer PEDF+DHA, promotes functional regeneration of damaged corneal nerves. Forty four-mer PEDF, by activating a corneal epithelial receptor, in conjunction with DHA could be a novel therapeutic agent for the treatment of neurotrophic keratitis and dry eye that develops as a result of corneal nerve damage.
authors.affiliation: Department of Ophthalmology and Neuroscience Center of Excellence School of Medicine, Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States.
authors.forename: Jiucheng
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Ophthalmology, University of Illinois Medical Center, Chicago, Illinois, United States.
authors.forename: M Soledad
authors.initials: MS
authors.lastname: Cortina
authors.affiliation: Department of Ophthalmology and Neuroscience Center of Excellence School of Medicine, Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States.
authors.forename: Azucena
authors.initials: A
authors.lastname: Kakazu
authors.affiliation: Department of Ophthalmology and Neuroscience Center of Excellence School of Medicine, Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States.
authors.forename: Haydee E P
authors.initials: HE
authors.lastname: Bazan
mesh_terms: D000818:Animals; D003315:Cornea / Q000294:innervation / Q000502:physiology*; D003319:Corneal Stroma / Q000601:surgery*; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D004847:Epithelial Cells / Q000378:metabolism; D019573:Epithelium, Corneal / Q000378:metabolism; D005136:Eye Proteins / Q000494:pharmacology*; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D009882:Ophthalmic Nerve / Q000293:injuries / Q000502:physiology*; D011817:Rabbits; D018013:Receptors, Neuropeptide / Q000378:metabolism; D015843:Serpins / Q000494:pharmacology*; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D004281:Docosahexaenoic Acids; D005136:Eye Proteins; D009414:Nerve Growth Factors; D018013:Receptors, Neuropeptide; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor; C400531:pigment epithelium-derived factor receptor