title: Capsaicin-induced corneal sensory denervation and healing impairment are reversed by NGF treatment.
abstract: OBJECTIVE
  We aimed to evaluate the nerve growth factor (NGF) pathway and its influence on corneal healing mechanisms in normal conditions and in an animal model of corneal denervation induced by capsaicin.
  
  
  METHODS
  Peripheral sensory damage was induced in rat pups by subcutaneous injection of capsaicin and the effects evaluated by hot-plate test, corneal nerve count, and tear secretion. Corneal damage was induced in capsaicin-treated and -untreated rats by epithelial scraping. Healing rate; NGF pathway (NGF, tyrosine kinase A [TrkA], p75); and the stem cell marker p63 were evaluated by RT-PCR, ELISA, Western blot, and immunohistochemistry. The effects of exogenous NGF administration as eye drop formulation were also tested.
  
  
  RESULTS
  Capsaicin treatment induced a significant reduction of peripheral sensitivity, corneal innervation, tear secretion, and corneal healing rate. The ocular effects of capsaicin treatment were associated with an NGF pathway alteration. NGF eye drop treatment aided corneal healing mechanisms through a significant increase in the NGF receptors TrkA and p75, and in the stem cell marker p63.
  
  
  CONCLUSIONS
  In this study, we show that an alteration in the NGF pathway is responsible for a delay in corneal healing in an animal model of sensory denervation. Moreover, we show that NGF eye drop administration modulates corneal innervation, epithelial cell healing, and corneal stem cells. These findings may trigger further research on the role of the NGF pathway in limbal stem cell deficiency.
authors.affiliation: Department of Ophthalmology, Campus Bio-Medico University of Rome, Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Lambiase
authors.forename: Luigi
authors.initials: L
authors.lastname: Aloe
authors.forename: Flavio
authors.initials: F
authors.lastname: Mantelli
authors.forename: Marta
authors.initials: M
authors.lastname: Sacchetti
authors.forename: Eleonora
authors.initials: E
authors.lastname: Perrella
authors.forename: Patrizia
authors.initials: P
authors.lastname: Bianchi
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Rocco
authors.forename: Stefano
authors.initials: S
authors.lastname: Bonini
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002211:Capsaicin / Q000633:toxicity*; D003315:Cornea / Q000294:innervation*; D065306:Corneal Injuries; D003389:Cranial Nerve Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D048049:Extracellular Signal-Regulated MAP Kinases; D005131:Eye Injuries / Q000188:drug therapy / Q000378:metabolism; D007150:Immunohistochemistry; D020932:Nerve Growth Factor / Q000627:therapeutic use*; D009419:Nerve Tissue Proteins; D009882:Ophthalmic Nerve / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020917:Receptor, trkA / Q000378:metabolism; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018689:Sensory System Agents / Q000633:toxicity; D013563:Sympathectomy, Chemical; D014945:Wound Healing / Q000187:drug effects*; D014949:Wounds, Nonpenetrating / Q000188:drug therapy / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor; D018689:Sensory System Agents; C068313:Ngfr protein, rat; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D048049:Extracellular Signal-Regulated MAP Kinases; C102548:Mapk4 protein, rat; D002211:Capsaicin