Cellular regeneration strategies for macular degeneration: past, present and future.
Cellular regeneration strategies for macular degeneration: past, present and future.
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DOI：
10.1038/s41433-018-0061-z
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发表时间：
2018-05
期刊：
影响因子：
--
通讯作者：
Steel DH
中科院分区：
文献类型：
--
作者：
Chichagova V;Hallam D;Collin J;Zerti D;Dorgau B;Felemban M;Lako M;Steel DH
尽管有相当大的努力和显著的治疗进展，老年性黄斑变性(AMD)仍然是发达国家最常见的失明原因。进行性晚期AMD伴视网膜外变性，目前尚无有效的治疗方法。细胞治疗可能减缓或逆转AMD的视力丧失，这一点引起了人们的极大兴趣。已经提出了许多行动模式，包括细胞替换和拯救，以及通过免疫调节来延缓神经退化过程。它们在这种神秘疾病中的吸引力与它们的普通、非途径特异性效应有关。尤其是外层视网膜，一直处于细胞再生疗法发展的前沿，可以通过手术获得，易于观察，并且具有相对简单的结构。视网膜色素上皮(RPE)和光感受器都被考虑作为薄膜和细胞悬浮液的替代疗法。使用自体RPE的研究，以及在较小程度上使用胎儿视网膜的研究，已经证明了这一原理。已经提出了各种各样的细胞来源，目前多能干细胞来源的细胞占据着中心舞台。最近使用这些细胞进行RPE替代的早期试验已经达到了安全终点，并暗示了可能的疗效。动物研究证实了光感受器替换的前景，即使是在完全退化的外层视网膜也可能恢复一些视力。然而，仍然存在许多挑战，尤其是包括避免免疫排斥、确保细胞长期存活和最大化效果。本审查概述了已取得的进展、正在进行的研究和未来的挑战。
Despite considerable effort and significant therapeutic advances, age-related macular degeneration (AMD) remains the commonest cause of blindness in the developed world. Progressive late-stage AMD with outer retinal degeneration currently has no proven treatment. There has been significant interest in the possibility that cellular treatments may slow or reverse visual loss in AMD. A number of modes of action have been suggested, including cell replacement and rescue, as well as immune modulation to delay the neurodegenerative process. Their appeal in this enigmatic disease relate to their generic, non-pathway-specific effects. The outer retina in particular has been at the forefront of developments in cellular regenerative therapies being surgically accessible, easily observable, as well as having a relatively simple architecture. Both the retinal pigment epithelium (RPE) and photoreceptors have been considered for replacement therapies as both sheets and cell suspensions. Studies using autologous RPE, and to a lesser extent, foetal retina, have shown proof of principle. A wide variety of cell sources have been proposed with pluripotent stem cell-derived cells currently holding the centre stage. Recent early-phase trials using these cells for RPE replacement have met safety endpoints and hinted at possible efficacy. Animal studies have confirmed the promise that photoreceptor replacement, even in a completely degenerated outer retina may restore some vision. Many challenges, however, remain, not least of which include avoiding immune rejection, ensuring long-term cellular survival and maximising effect. This review provides an overview of progress made, ongoing studies and challenges ahead.
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