title: Spontaneous chronic corneal epithelial defects (SCCED) in dogs: clinical features, innervation, and effect of topical SP, with or without IGF-1.
abstract: OBJECTIVE
  To delineate the clinical features and alterations in innervation and substance P (SP) content in spontaneous chronic corneal epithelial defects (SCCED) in dogs and to conduct a preliminary investigation evaluating the efficacy of topical SP, with or without insulin-like growth factor (IGF)-1, in the treatment of this disorder.
  
  
  METHODS
  Complete ophthalmic examinations, including Cochet-Bonnet aesthesiometry, were performed in 45 canine patients that had spontaneous corneal epithelial defects of at least 3 weeks' duration and with no identifiable cause. Eighteen patients had superficial keratectomies performed, and the corneal nerves were labeled immunohistochemically with antibodies against protein gene product (PGP)-9.5, SP, vasoactive intestinal peptide (VIP), and tyrosine hydroxylase (TH). Relative fiber densities were assessed qualitatively and quantitatively. Corneal epithelial cell and tear SP contents were determined in affected and normal dogs by an enzyme immunoassay. A preliminary open-label treatment trial of topical SP, with and without IGF-1, was conducted in 21 dogs.
  
  
  RESULTS
  The duration of the erosion before admittance into the study was a mean of 9.22 weeks (range, 3-52). The average patient was middle aged (mean, 9.25 +/- 1.85 years [SD]); no sex predisposition of the disease was identified. Boxers, golden retrievers, and keeshonds were overrepresented when compared with the normal hospital population. Corneal sensation was normal. Marked alterations in corneal innervation were identified in affected dogs with abnormal increased SP and calcitonin gene-related peptide (CGRP)-immunoreactive nerve plexuses identified surrounding the periphery of the epithelial defect. The SP content of epithelial cells surrounding the defect increased, whereas the tear SP content remained unchanged. Of the canine patients treated with SP, with or without IGF-1, 70% to 75% had complete healing of the defect.
  
  
  CONCLUSIONS
  This idiopathic spontaneous corneal disease in dogs shares clinical features with chronic epithelial defects in humans. The presence of marked alterations in peptidergic innervation and positive response to topical therapy with SP suggest that SP plays a critical role in corneal wound-healing processes.
authors.affiliation: Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 53706, USA. murphyc@svm.vetmed.wisc.edu
authors.forename: C J
authors.initials: CJ
authors.lastname: Murphy
authors.forename: C F
authors.initials: CF
authors.lastname: Marfurt
authors.forename: A
authors.initials: A
authors.lastname: McDermott
authors.forename: E
authors.initials: E
authors.lastname: Bentley
authors.forename: G A
authors.initials: GA
authors.lastname: Abrams
authors.forename: T W
authors.initials: TW
authors.lastname: Reid
authors.forename: S
authors.initials: S
authors.lastname: Campbell
mesh_terms: D000287:Administration, Topical; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002908:Chronic Disease; D003316:Corneal Diseases / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism / Q000662:veterinary*; D004283:Dog Diseases / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism; D004285:Dogs; D004359:Drug Therapy, Combination; D019573:Epithelium, Corneal / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015590:Fluorophotometry / Q000662:veterinary; D007124:Immunoenzyme Techniques / Q000662:veterinary; D007334:Insulin-Like Growth Factor I / Q000627:therapeutic use*; D008297:Male; D013373:Substance P / Q000378:metabolism / Q000627:therapeutic use*; D013869:Thiolester Hydrolases / Q000378:metabolism; D014276:Trigeminal Nerve / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D043222:Ubiquitin Thiolesterase; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
chemical_list: D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D007334:Insulin-Like Growth Factor I; D014446:Tyrosine 3-Monooxygenase; D013869:Thiolester Hydrolases; D043222:Ubiquitin Thiolesterase; D015740:Calcitonin Gene-Related Peptide