| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Research Abstract |
The purpose of this study is to elucidate the effect of semaphorin3A inhibitor as a potential therapeutic agent. Penetrating keratoplasty requires a full-thickness 360°corneal incision that cuts corneal nerves and results in complete denervation of the graft. Several studies have reported a marked reduction in corneal sensation after penetrating keratoplasty, and it requires many years to recover the corneal sensation. Recent research has demonstrated that semaphorin3A (Sema3A) is one of the major inhibitors of axonal regeneration, and strong semaphorin3A inhibitor enhances regenerative responses of the injured spinal cord on rats.
P0-Cre/Floxed-EGFP mice, whose keratocytes, endothelial cells and nerves in corneas express GFP, was used as a recipient of corneal transplantation, and the syngeneic wild-type mouse cornea was used as a donor. The Sema3A inhibitor was administered every two days by subconjunctival injection. To the control group, only its solvent without the inhibitor was administered. They were followed up for three weeks postoperatively. Corneal sensitivity, length of nerves and neovessels in the corneal grafts were evaluated.
In the mouse corneal transplantation model, nerve regeneration into the grafts was significantly facilitated in the Sema3A inhibitor administered group compared to the control group. It was also revealed in the Sema3A inhibitor administrated group that corneal sensitivity was improved and that functions of nerves were recovered. Although nerve regeneration into corneal grafts was successfully facilitated by administering the Sema3A inhibitor, more detailed examination is necessary, e. g., in order to elucidate physiological action of Sema3A in corneas, and lack of neovascularization even by the Sema3A inhibitor.
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