title: Vascular endothelial growth factor promotes anatomical and functional recovery of injured peripheral nerves in the avascular cornea.
abstract: Peripheral nerve injury is a major neurological disorder that can cause severe motor and sensory dysfunction. Neurogenic effects of vascular endothelial growth factor (VEGF) have been found in the central nervous system, and we examined whether VEGF could promote anatomical and functional recovery of peripheral nerves after injury using an avascular corneal nerve injury model. We found that VEGF enhanced neurite elongation in isolated trigeminal ganglion neurons in a dose-dependent manner. This effect was suppressed by neutralizing antibodies for VEGF receptor (VEGFR) 1 and 2 or neuropilin receptor 1 or by VEGFR2 inhibitors (SU 1498 and Ki 8751). In vivo, mice receiving sustained VEGF via implanted pellets showed increased corneal nerve regeneration after superficial injury compared with those receiving vehicle. VEGF injected subconjunctivally at the time of injury accelerated reinnervation, the recovery of mechanosensation, and epithelial wound healing. Endogenous VEGF expression was up-regulated in the corneal epithelium and stroma after wounding. Thus, VEGF can mediate peripheral neuron growth but requires the activation of multiple VEGF receptor types. In addition, VEGF can accelerate the return of sensory and trophic functions of damaged peripheral nerves. Wounding induces the expression of VEFG, which may modulate physiological nerve repair.
authors.affiliation: Margaret M. Dyson Vision Research Institute, Department of Ophthalmology, Weill Cornell Medical College, 1300 York Ave., New York, NY 10065, USA.
authors.forename: Zan
authors.initials: Z
authors.lastname: Pan
authors.forename: Shima
authors.initials: S
authors.lastname: Fukuoka
authors.forename: Natalia
authors.initials: N
authors.lastname: Karagianni
authors.forename: Victor H
authors.initials: VH
authors.lastname: Guaiquil
authors.forename: Mark I
authors.initials: MI
authors.lastname: Rosenblatt
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000494:pharmacology; D002478:Cells, Cultured; D002934:Cinnamates / Q000494:pharmacology; D003315:Cornea / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D059348:Peripheral Nerve Injuries / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D010671:Phenylurea Compounds / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D020127:Recovery of Function / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012668:Trigeminal Ganglion / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D057134:Antibodies, Neutralizing; D002934:Cinnamates; C499138:N-(2,4-difluorophenyl)-N'-(4-((6,7-dimethoxy-4-quinolyl)oxy)-2-fluorophenyl)urea; D010671:Phenylurea Compounds; D011804:Quinolines; C483044:SU 1498; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor
keywords: eye; nerve regeneration; neurofluorescent thy1-YFP mice; neurotrophic; receptor; wound healing