Protection of photoreceptor cells from phototoxicity by transplanted retinal pigment epithelial cells expressing different neurotrophic factors
Protection of photoreceptor cells from phototoxicity by transplanted retinal pigment epithelial cells expressing different neurotrophic factors
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DOI：
10.3727/000000005783982549
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发表时间：
2005-01-01
影响因子：
3.3
通讯作者：
Tamai, M
中科院分区：
文献类型：
--
作者：
Abe, T;Saigo, Y;Tamai, M
细胞或组织的移植和神经营养因子的玻璃体内注射是已经用于治疗视网膜疾病的两种方法。本研究的目的是检查结合两种方法的效果：视网膜色素上皮（RPE）细胞表达不同的神经营养因子的移植。神经营养因子为Axokine、脑源性神经营养因子（BDNF）和碱性成纤维细胞生长因子（bFGF）。增强型绿色荧光蛋白（eGFP）基因被用作报告基因。通过脂质体转染法将这些基因导入RPE细胞，经抗生素筛选后，移植到108只大鼠的视网膜下腔。在移植后1周和3个月对大鼠进行检查，以确定转导细胞是否存在，是否表达蛋白质，以及是否能够保护光感受器免受光毒性。通过eGFP的存在监测移植细胞的存活。保护程度由外核层的厚度决定。我们的结果表明，不同类型的神经营养因子在1周时对感光细胞的保护程度不同。3个月后，存活的移植细胞数量显著减少，并且仅用BDNF转导的RPE细胞观察到保护作用。在早期和晚期，在视网膜的非移植区域也观察到BDNF转导的RPE细胞的显著程度的拯救。玻璃体、视网膜和脉络膜在任何时间均未检测到淋巴细胞浸润。我们得出的结论是，移植携带BDNF基因的RPE细胞可以减轻移植区光毒性引起的感光细胞损伤，而非移植区的光毒性损伤则较弱。
Transplantation of cells or tissues and the intravitreal injection of neurotrophic factors are two methods that have been used to treat retinal diseases. The purpose of this study was to examine the effects of combining both methods: the transplantation of retinal pigment epithelial (RPE) cells expressing different neurotrophic factors. The neutrophic factors were Axokine, brain derived-neurotrophic factor (BDNF), and basic fibroblast growth factor (bFGF). The enhanced green fluorescence protein (eGFP) gene was used as a reporter gene. These genes were transduced into RPE cells by lipofection, selected by antibiotics, and transplanted into the subretinal space of 108 rats. The rats were examined at 1 week and 3 months after the transplantation to determine whether the transduced cells were present, were expressing the protein, and were able to protect photoreceptors against phototoxicity. The survival of the transplanted cells was monitored by the presence of eGFP. The degree of protection was determined by the thickness of the outer nuclear layer. Our results showed that the degree of photoreceptor protection was different for the different types of neurotrophic factors at 1 week. After 3 months, the number of surviving transplanted cell was markedly reduced, and protection was observed only with the BDNF-transduced RPE cells. A significant degree of rescue was also observed by BDNF-transduced RPE cells in the nontransplanted area of the retina at both the early and [ate times. Lymphocytic infiltration was not detected in the vitreous, retina, and choroid at any time. We conclude that the transplantation of BDNF-transduced RPE cells can reduce the photoreceptor damage induced by phototoxicity in the transplanted area and weakly in the nontransplanted area.