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J.-W. Jang, H. Lim, Y. Cho, O.-W. Kwon, D.-S. Kim; BMP-7 Induces Wound Healing Without Neovascularization and Opacification in a Corneal Alkali Injured Mouse Model. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4549.
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An alkali burn in the cornea is a common serious clinical problem often leading to permanent visual impairment. We verified the scar-less wound healing effects of BMP-7 on corneal alkali burn in our previous studies. However, some have reported that BMP-7 is not effective for therapeutic administration, because it induces unexpected angiogenesis. In this study, we find the optimal therapeutic dose of BMP-7 which induces scar-less wound healing without angiogenic side effect.
Corneal alkali burn was induced with 0.15 N-NaOH in both eyes of the anesthesized mice by ketamine and topical proparacaine. The right eyes were respectively treated with 1.25, 0.5 or 0.25 ng of BMP-7, four times a day for 5 days (total 25, 10 or 5 ng). The left were treated with only vehicle as control. The corneas were then weekly observed by biomicroscopy, and scored by opacification and haemorrhage. The neovascularization was also observed by fluorescent microscopy. At same time, eye tissue-sections were histopathologically evaluated by H&E staining and immunohistochemistry of fibronectin.
Topical 10 ng of BMP-7 significantly accelerated proliferation of corneal epithelium without the side-effects like a neovascularization, haemorrhage and opacification. The 25 ng of BMP-7 also induced the accelerated cell proliferation, but did not sufficiently inhibit stromal opacification and neovascularization. In addition, any attenuation of the side-effects was not observed, and healing evidences in the 5 ng of BMP-7 treated eyes. In the 10 ng or 25 ng of BMP-7 administrated eyes, fibronectin, roles as a key-factor in scar formation, was significantly attenuated compared with the control.
This result shows that application of the dose range between 10 ng and 25 ng of BMP-7 induces effective corneal wound healing without angiogenic side effects. We supposed the reason which the dose of BMP-7 has not influence on the up-regulated growth factors in the injured cornea. Therefore, we suggest that the low dose (≈ 10 ng) of BMP-7 would be useful as therapeutics to accelerate wound healing without side effects such as neovascularization, haemorrhage, opacification and scarring in injured cornea.
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