title: VEGF-B selectively regenerates injured peripheral neurons and restores sensory and trophic functions.
abstract: VEGF-B primarily provides neuroprotection and improves survival in CNS-derived neurons. However, its actions on the peripheral nervous system have been less characterized. We examined whether VEGF-B mediates peripheral nerve repair. We found that VEGF-B induced extensive neurite growth and branching in trigeminal ganglia neurons in a manner that required selective activation of transmembrane receptors and was distinct from VEGF-A-induced neuronal growth. VEGF-B-induced neurite elongation required PI3K and Notch signaling. In vivo, VEGF-B is required for normal nerve regeneration: mice lacking VEGF-B showed impaired nerve repair with concomitant impaired trophic function. VEGF-B treatment increased nerve regeneration, sensation recovery, and trophic functions of injured corneal peripheral nerves in VEGF-B-deficient and wild-type animals, without affecting uninjured nerves. These selective effects of VEGF-B on injured nerves and its lack of angiogenic activity makes VEGF-B a suitable therapeutic target to treat nerve injury.
authors.affiliation: Margaret M. Dyson Vision Research Institute, Department of Ophthalmology, Weill Cornell Medical College, New York, NY 10065.
authors.forename: Victor H
authors.initials: VH
authors.lastname: Guaiquil
authors.affiliation: Margaret M. Dyson Vision Research Institute, Department of Ophthalmology, Weill Cornell Medical College, New York, NY 10065.
authors.forename: Zan
authors.initials: Z
authors.lastname: Pan
authors.affiliation: Margaret M. Dyson Vision Research Institute, Department of Ophthalmology, Weill Cornell Medical College, New York, NY 10065.
authors.forename: Natalia
authors.initials: N
authors.lastname: Karagianni
authors.affiliation: Margaret M. Dyson Vision Research Institute, Department of Ophthalmology, Weill Cornell Medical College, New York, NY 10065.
authors.forename: Shima
authors.initials: S
authors.lastname: Fukuoka
authors.affiliation: Margaret M. Dyson Vision Research Institute, Department of Ophthalmology, Weill Cornell Medical College, New York, NY 10065.
authors.forename: Gemstonn
authors.initials: G
authors.lastname: Alegre
authors.affiliation: Margaret M. Dyson Vision Research Institute, Department of Ophthalmology, Weill Cornell Medical College, New York, NY 10065 mrosenbl@uic.edu.
authors.forename: Mark I
authors.initials: MI
authors.lastname: Rosenblatt
mesh_terms: D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D003315:Cornea / Q000187:drug effects* / Q000294:innervation / Q000503:physiopathology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D009416:Nerve Regeneration / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D016501:Neurites / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D059348:Peripheral Nerve Injuries / Q000235:genetics / Q000503:physiopathology; D010525:Peripheral Nerves / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012668:Trigeminal Ganglion / Q000166:cytology; D042561:Vascular Endothelial Growth Factor B / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism
chemical_list: D051880:Receptors, Notch; D042561:Vascular Endothelial Growth Factor B; D019869:Phosphatidylinositol 3-Kinases; D040281:Vascular Endothelial Growth Factor Receptor-1; D051057:Proto-Oncogene Proteins c-akt
keywords: VEGF-B; cornea; nerve injury; neuronal growth