TREATMENT OF RETINAL DEGENERATIVE DISIESE BY TRANSPLANTATION OF GENE TRANSFERRED CELLS

我们的研究目的是通过在视网膜下空间移植细胞来治疗视网膜退行性疾病，这些细胞通过转移有效的抑制光感受器变性的基因来修饰。为了达到这个目的，我们计划使用虹膜色素上皮细胞（IPE）作为移植细胞的候选细胞。使用IPE细胞的优点是可以进行自体细胞移植。体外培养的IPE细胞易于从眼内获得并维持。将该基因体外转移到IPE细胞中，对光感受器变性具有保护作用，使得仅转移靶细胞成为可能。三年来，我们明确了以下五件事：IPE细胞与视网膜色素上皮细胞具有相似的性质。2. 将IPE细胞移植到视网膜下间隙时，IPE细胞在移植区存活了6个月。3. 移植的IPE细胞具有与RPE细胞相同的吞噬活性，表明移植的IPE细胞在视网膜下空间起作用。4. 我们没有发现IPE移植引起的不良反应。5. 已有报道用腺病毒载体进行基因转移可引起全身性感染并引起炎症反应。我们的研究表明，即使使用腺病毒载体进行基因转染，体外转移基因也可能使全身感染率降低。然而，考虑到表达周期和不良反应，我们发现腺相关病毒载体对基因转移是有用的。BDNF移植的IPE细胞对光毒性或谷氨酸毒性所致的视网膜变性具有保护作用。

Our purpose of this research is to treat retinal degenerative diseise by transplanting cells in the sub retinal space which are modified by transferring effective gene for inhibition of photoreceptor degeneration. To achieve this purpose, we were planning to use the iris pigment epithelial (IPE) cells as a candidate for the transplanting cells. The advantage of using IPE cells is to be possible to do the autolougous cell transplantation. IPE cells could be obtained from the eye easily and maintain under the culture. To transfer the gene to IPE cells in vitro which has the protective effect on the photoreceptor degeneration makes possible to transfer the target cells only.We have clarified below five things for 3 years.1. IPE cell has similar properties with the retinal pigernent epithelial cells. 2. When IPE cells were transplanted into sub retinal space, IPE cells have been survived in the transplanted area for 6 months. 3. The transplanted IPE cells had the phagocytic activity like RPE cells, which indicated transplanted IPE cells functionally worked in sub-retinal space. 4. We could not any adverse effect caused by the IPE transplantation. 5. It has been reported adenovirus caused systemic infection which induced inflammatory response when adenovirus vector was used for the gene transfer. Our study showed possibilities that in vitro transfer of gene made systemic infection rate decrease even if the adenovirus vector was used for the gene transfection. However we found that adeno-associated virus vector were useful for the gene transfer in view of expression periods and adverse effect. The transplantation of BDNF transferred IPE cells has protective effects on retinal degeneration induced by light or glutamate toxicity.