Cell replacement and visual restoration by retinal sheet transplants.

Cell replacement and visual restoration by retinal sheet transplants.
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DOI:
10.1016/j.preteyeres.2012.06.003
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发表时间:
2012-11
影响因子:
17.8
通讯作者:
Aramant RB
Aramant RB
中科院分区:
医学1区
文献类型:
--
作者:
Seiler MJ;Aramant RB

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视网膜疾病,如老年性黄斑变性(ARMD)和视网膜色素变性(RP),影响着数百万人。用与宿主视网膜仍有功能的部分相连的新细胞来取代丢失的细胞,可能会修复退化的视网膜,并在未知的程度上恢复视力。一种独特的模式,即新鲜解剖的胎儿视网膜前体细胞与其视网膜色素上皮(RPE)相结合的视网膜下移植,已在动物和人类中证明了成功的结果。大多数其他方法仅限于在疾病早期抢救受者的内源性视网膜细胞,而不是针对神经视网膜细胞的替代。片状移植修复了几种视网膜变性模型中与移植在视网膜中的位置相对应的上丘(SC)中丢失的视觉反应。它们不只是保持视觉性能--它们提高了对光线的视觉反应。SC中视觉反应的恢复可以直接追溯到移植中的神经细胞,表明移植和宿主之间的突触联系有助于视觉的改善。移植过程侵入宿主视网膜的内丛状层,并与可能的宿主细胞形成突触。在对RP和ARMD患者进行的II期试验中,视网膜移植及其RPE改善了视力。总之,视网膜祖细胞片移植提供了一个很好的模型来回答如何修复和恢复退化的视网膜功能的问题。胎儿供体组织的供应总是有限的,但该模型可以为最佳的细胞替代疗法设定标准并提供信息基础,例如胚胎干细胞(ESC)衍生疗法。
Retinal diseases such as age-related macular degeneration (ARMD) and retinitis pigmentosa (RP) affect millions of people. Replacing lost cells with new cells that connect with the still functional part of the host retina might repair a degenerating retina and restore eyesight to an unknown extent. A unique model, subretinal transplantation of freshly dissected sheets of fetal-derived retinal progenitor cells, combined with its retinal pigment epithelium (RPE), has demonstrated successful results in both animals and humans. Most other approaches are restricted to rescue endogenous retinal cells of the recipient in earlier disease stages by a ‘nursing’ role of the implanted cells and are not aimed at neural retinal cell replacement. Sheet transplants restore lost visual responses in several retinal degeneration models in the superior colliculus (SC) corresponding to the location of the transplant in the retina. They do not simply preserve visual performance – they increase visual responsiveness to light. Restoration of visual responses in the SC can be directly traced to neural cells in the transplant, demonstrating that synaptic connections between transplant and host contribute to the visual improvement. Transplant processes invade the inner plexiform layer of the host retina and form synapses with presumable host cells. In a Phase II trial of RP and ARMD patients, transplants of retina together with its RPE improved visual acuity. In summary, retinal progenitor sheet transplantation provides an excellent model to answer questions about how to repair and restore function of a degenerating retina. Supply of fetal donor tissue will always be limited but the model can set a standard and provide an informative base for optimal cell replacement therapies such as embryonic stem cell (ESC)-derived therapy.
DOI: 10.1016/j.visres.2009.04.008
发表时间: 2009-11
期刊: VISION RESEARCH
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