Doudet D J, Cornfeldt M L, Honey C R, Schweikert A W, Allen R C
Pacific Parkinson Research Centre, Department of Medicine/Neurology, University of British Columbia, Vancouver, BC, Canada V6T 2B5.
Exp Neurol. 2004 Oct;189(2):361-8. doi: 10.1016/j.expneurol.2004.06.009.
Human retinal pigment epithelial (hRPE) cells produce L-dopa, are easily harvested and expanded in culture, and, attached to microcarriers, can survive in the brain without immunosuppression. Studies in rats, primates, and parkinsonian patients have demonstrated that striatally implanted hRPE cells attached to gelatin microcarriers (RPE-GM) are able to improve parkinsonian symptoms and are well tolerated for extended periods. In moderately to severely impaired monkeys with bilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-induced parkinsonism receiving a unilateral RPE-GM implant in the putamen, there was a 39% improvement in clinical scores over the first 2 months post-implant. Positron emission tomography (PET) with [18F]fluoro-L-dopa (FDOPA) showed increased accumulation in the implanted putamen and a concomitant decrease in [11C]raclopride binding in the same area, suggesting increased dopamine release compared to the contralateral putamen. We report the first in vivo visualization of hRPE cells and their effects, implicating a dopaminergic mechanism of action.
人视网膜色素上皮（hRPE）细胞可产生L-多巴，易于采集并在培养中扩增，且附着于微载体后，无需免疫抑制就能在脑内存活。对大鼠、灵长类动物及帕金森病患者的研究表明，纹状体内植入附着于明胶微载体的hRPE细胞（RPE-GM）能够改善帕金森病症状，且在较长时间内耐受性良好。在因双侧盐酸1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的帕金森病而导致中度至重度功能受损的猴子中，单侧壳核植入RPE-GM后，植入后前2个月临床评分改善了39%。用[18F]氟-L-多巴（FDOPA）进行正电子发射断层扫描（PET）显示，植入的壳核中放射性积聚增加，且同一区域内[11C]雷氯必利结合减少，这表明与对侧壳核相比，多巴胺释放增加。我们报告了hRPE细胞及其作用的首次体内可视化，提示存在多巴胺能作用机制。
