title: Neuroprotectin D1 restores corneal nerve integrity and function after damage from experimental surgery.
abstract: OBJECTIVE
  To investigate if topical treatment of neuroprotectin D1 (NPD1) increases regeneration of functional nerves after lamellar keratectomy.
  
  
  METHODS
  An 8-mm stromal dissection was performed in the left eye of each rabbit. The rabbits were treated with NPD1, pigment epithelial-derived factor (PEDF) in combination with docosahexaenoic acid (DHA) or vehicle for 6 weeks, and corneas were obtained at 8 weeks. After fixation, corneal wholemounts were stained with mouse monoclonal anti-βIII-tubulin antibody and double stained with chicken anti-calcitonin gene-related peptide (CGRP) antibody. Corneal sensitivity and tear secretion were measured using the Cochet-Bonnet esthesiometer and the Schirmer's test, respectively. Additional rabbits were treated with NPD1, PEDF+DHA, or vehicle, and corneal sections were stained with a rat monoclonal anti-neutrophil antibody. Cultures of trigeminal ganglia from 5-day-old mice were treated with NPD1, PEDF+DHA, lipoxin A4 (LXA4), 12- or 15-hydroxyeicosatetraenoic acid (12[S] or 15[S]-HETE), and nerve growth factor (NGF) as positive control.
  
  
  RESULTS
  NPD1 increased subepithelial corneal nerve area three times compared with vehicle-treated rabbits. The effect was similar to PEDF+DHA-treated animals. There was recovery of CGRP-positive neurons and an increase in corneal sensitivity and tear secretion in NPD1-treated animals. NPD1 decreased neutrophil infiltration after 2 and 4 days of treatment. In the in vitro cultures, NPD1 and PEDF+DHA induced a 3-fold increase in neurite outgrowth compared with cultures without supplementation. Treatments with LXA4, 12(S)-, and 15(S)- HETE did not stimulate neurite outgrowth.
  
  
  CONCLUSIONS
  NPD1 has anti-inflammatory and nerve regenerative properties. This study demonstrates that NPD1 may offer an effective treatment for neurotrophic corneas.
authors.affiliation: Department of Ophthalmology, University of Illinois Medical Center, Chicago, Illinois, USA.
authors.forename: Maria Soledad
authors.initials: MS
authors.lastname: Cortina
authors.forename: Jiucheng
authors.initials: J
authors.lastname: He
authors.forename: Tiffany
authors.initials: T
authors.lastname: Russ
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; D001369:Axons / Q000502:physiology; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002478:Cells, Cultured; D003315:Cornea / Q000294:innervation*; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004338:Drug Combinations; D005136:Eye Proteins / Q000494:pharmacology; D019084:Fluorescent Antibody Technique, Indirect; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology; D009416:Nerve Regeneration / Q000187:drug effects*; D016501:Neurites / Q000502:physiology; D009882:Ophthalmic Nerve / Q000502:physiology*; D011817:Rabbits; D051381:Rats; D015843:Serpins / Q000494:pharmacology; D013666:Tears / Q000502:physiology; D012668:Trigeminal Ganglion / Q000166:cytology / Q000187:drug effects; D014404:Tubulin / Q000378:metabolism; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D015740:Calcitonin Gene-Related Peptide; D004281:Docosahexaenoic Acids; D004338:Drug Combinations; D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D014404:Tubulin; D000099174:Pigment Epithelium-Derived Factor; C487679:protectin D1
keywords: corneal sensitivity; dry eye; neuroprotectin D1; neuroregeneration; pigment epithelial-derived factor