title: Therapeutic effects of adenoviral gene transfer of bone morphogenic protein-7 on a corneal alkali injury model in mice.
abstract: An alkali burn in the cornea is a common serious clinical problem often leading to permanent visual impairment. Since transforming growth factor-beta (TGF-beta) is involved in the response to corneal injury, we evaluated the therapeutic effects of adenoviral gene transfer of mouse bone morphogenic protein-7 (BMP-7), which has antagonistic effects on TGF-beta in tissue fibrosis. Burned cornea did not express endogenous BMP-7 mRNA and protein. Resurfacing of the burned cornea by invading conjunctival epithelium was accelerated by adenoviral introduction of BMP-7. Exogenous BMP-7 expression also suppressed myofibroblast generation, appearance of monocytes/macrophages and expression of MCP-1, TGF-betas, and collagen I alpha2 chain in the affected stroma. Ectopic BMP-7 did not suppress stromal neovascularization throughout the interval studied and also did not reduce VEGF mRNA expression at Day 10. Ectopic BMP-7 in burned corneal tissue resulted in activation of Smad1/5/8 signaling and partial suppression of the phospho-Smad2 signal. These data suggest that overexpression of BMP-7 is an effective strategy for treatment of ocular alkali burns.
authors.affiliation: Department of Ophthalmology, Wakayama Medical University, Kimiidera, Wakayama, Japan. shizuya@wakayama-med.ac.jp
authors.forename: Shizuya
authors.initials: S
authors.lastname: Saika
authors.forename: Kazuo
authors.initials: K
authors.lastname: Ikeda
authors.forename: Osamu
authors.initials: O
authors.lastname: Yamanaka
authors.forename: Kathleen C
authors.initials: KC
authors.lastname: Flanders
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakajima
authors.forename: Takeshi
authors.initials: T
authors.lastname: Miyamoto
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Ohnishi
authors.forename: Winston W-Y
authors.initials: WW
authors.lastname: Kao
authors.forename: Yasuteru
authors.initials: Y
authors.lastname: Muragaki
authors.forename: Akira
authors.initials: A
authors.lastname: Ooshima
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D002455:Cell Division; D003316:Corneal Diseases / Q000473:pathology / Q000628:therapy*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D005131:Eye Injuries / Q000473:pathology / Q000628:therapy*; D018014:Gene Transfer Techniques; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051785:Smad Proteins; D051898:Smad1 Protein; D015534:Trans-Activators / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics*
chemical_list: D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D051785:Smad Proteins; D051898:Smad1 Protein; C497401:Smad1 protein, mouse; D015534:Trans-Activators; D016212:Transforming Growth Factor beta