Retinal pigment epithelial cells secrete neurotrophic factors and synthesize dopamine: possible contribution to therapeutic effects of RPE cell transplantation in Parkinson's disease.
Retinal pigment epithelial cells secrete neurotrophic factors and synthesize dopamine: possible contribution to therapeutic effects of RPE cell transplantation in Parkinson's disease.
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视网膜色素上皮细胞分泌神经营养因子并合成多巴胺：可能有助于 RPE 细胞移植治疗帕金森病的疗效。
DOI：
10.1186/1479-5876-7-53
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发表时间：
2009-06-28
影响因子：
7.4
通讯作者：
Le, Weidong
中科院分区：
文献类型：
--
作者：
Ming, Ming;Li, Xuping;Fan, Xiaolan;Yang, Dehua;Li, Liang;Chen, Sheng;Gu, Qing;Le, Weidong
治疗帕金森病 (PD) 的新策略已从多巴胺 (DA) 替代转向黑质纹状体系统的再生或恢复。使用人视网膜色素上皮（RPE）细胞替代退化的多巴胺能（DAergic）神经元的细胞疗法已经被开发出来，并在PD的临床治疗中显示出良好的前景，但该疗法的确切机制尚未完全阐明。在本研究中，我们研究了这种疗法的有益效果是否与 RPE 细胞的营养特性及其合成 DA 的能力有关。我们评估了培养的 RPE 细胞的条件培养基 (CM) 对 DAergic 细胞对抗 6-羟基多巴胺 (6-OHDA) 和鱼藤酮诱导的神经毒性的保护作用，并测定了 RPE 细胞释放的胶质细胞源性神经营养因子 (GDNF) 和脑源性神经营养因子 (BDNF) 的水平。我们还测量了 DA 的合成和释放。最后，我们将微载体-RPE细胞移植到6-OHDA损伤的大鼠中，并观察阿朴吗啡诱导的旋转（AIR）的改善。我们在此报告：（1）来自RPE细胞的CM可以分泌营养因子GDNF和BDNF，并保护DAergic神经元免受6-OHDA和鱼藤酮诱导的细胞损伤； (2)培养的RPE细胞表达L-多巴脱羧酶(DDC)并合成DA； (3) 附着在微载体上的RPE细胞可以在宿主纹状体中存活并改善6-OHDA损伤的PD动物模型中的AIR； (4)在RPE细胞移植组织中GDNF和BDNF水平显着升高。这些发现表明RPE细胞具有分泌GDNF和BDNF并合成DA的能力，这可能有助于RPE细胞移植对PD的治疗效果。
New strategies for the treatment of Parkinson's disease (PD) are shifted from dopamine (DA) replacement to regeneration or restoration of the nigro-striatal system. A cell therapy using human retinal pigment epithelial (RPE) cells as substitution for degenerated dopaminergic (DAergic) neurons has been developed and showed promising prospect in clinical treatment of PD, but the exact mechanism underlying this therapy is not fully elucidated. In the present study, we investigated whether the beneficial effects of this therapy are related to the trophic properties of RPE cells and their ability to synthesize DA. We evaluated the protective effects of conditioned medium (CM) from cultured RPE cells on the DAergic cells against 6-hydroxydopamine (6-OHDA)- and rotenone-induced neurotoxicity and determined the levels of glial cell derived neurotrophic factor (GDNF) and brain derived neurotrophic factor (BDNF) released by RPE cells. We also measured the DA synthesis and release. Finally we transplanted microcarriers-RPE cells into 6-OHDA lesioned rats and observed the improvement in apomorphine-induced rotations (AIR). We report here: (1) CM from RPE cells can secret trophic factors GDNF and BDNF, and protect DAergic neurons against the 6-OHDA- and rotenone-induced cell injury; (2) cultured RPE cells express L-dopa decarboxylase (DDC) and synthesize DA; (3) RPE cells attached to microcarriers can survive in the host striatum and improve the AIR in 6-OHDA-lesioned animal model of PD; (4) GDNF and BDNF levels are found significantly higher in the RPE cell-grafted tissues. These findings indicate the RPE cells have the ability to secret GDNF and BDNF, and synthesize DA, which probably contribute to the therapeutic effects of RPE cell transplantation in PD.
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影响因子：
11.2
作者：
Olanow, CW;Goetz, CG;Freeman, TB
通讯作者：
Freeman, TB
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