Therapeutic effects of adenoviral gene transfer of bone morphogenic protein-7 on a corneal alkali injury model in mice.
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.
Saika
Shizuya
S
Department of Ophthalmology, Wakayama Medical University, Kimiidera, Wakayama, Japan. shizuya@wakayama-med.ac.jp
Ikeda
Kazuo
K
Yamanaka
Osamu
O
Flanders
Kathleen C
KC
Nakajima
Yuji
Y
Miyamoto
Takeshi
T
Ohnishi
Yoshitaka
Y
Kao
Winston W-Y
WW
Muragaki
Yasuteru
Y
Ooshima
Akira
A
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*
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