2012 Fiscal Year Final Research Report
vascular invasion and cultivated oral mucosal epithelial sheets
| Project/Area Number |
22591951
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Ophthalmology
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| Research Institution | Tokyo Dental College |
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Principal Investigator |
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| Project Period (FY) |
2010 – 2012
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| Keywords | 移植・再生医療 / 眼表面再建 / 血管新生 |
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| Research Abstract |
Transplantation of cultivated oral mucosal epithelial sheets is one of the surgical procedures to reconstruct ocular surface in patients with limbal stem cell deficiency. The major advantage of this treatment is the absence of the need for postoperative immunosuppressive therapy. There are two types of cultivated oral mucosal epithelial sheets with or without amniotic membrane as a substrate. Since vascular invasion underneath transplanted sheet, which might cause decreased visual acuities were common in cases of the transplantation of cultivated oral mucosal epithelium sheets with a substrate during postoperative courses, this finding was considered a possibility of the existence substrate is involved in the pathogenesis. First, I examined the relationship between the existence of substrate and the expression of angiogeneic growth factors and angiogenesis inhibitors in cultivated oral mucosal epithelial sheets. There was no difference of the expression of these factors at both transcr
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iption and protein level. Next, the histopathological examination of corneal tissue harvested at the time of secondary keratoplasty following the transplantation of cultivated oral mucosal epithelial transplantation, and examined was performed. Each pathological finding had strong influence of microenvironment of ocular surface, and it was in the difficult situation to confirm the influence by the existence of a substrate. Therefore, we examined histopathologically the prognosis of cultivated epithelial sheets prepared from rabbitoral mucosa by using the rabbit model of limbus stem cell dysfunction. Cultivated epithelial sheets without substrate obtained good adhesion to corneal stroma and smooth ocular surface. On the other hand, cultivated epithelial sheets with substrate had low adhesion and epithelial cell invasion and vascular invasion accompanied with fibrosis from the peripheral underneath transplanted epithelial sheets were observed. Similar findings of vascular invasion underneath transplanted oral mucosal epithelial sheets also obtained in rabbit model. These data suggests the adhesiveness with transplanted oral mucosal epithelial sheets and corneal stroma may cause the vascular invasion underneath transplanted sheets. Less
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