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Nature:再生技术让盲鼠复明 为治疗视网膜色素变性等致盲疾病带来希望

2018-08-21 赵熙熙 中国科学报

人眼中有一些细胞能够修复视力受损疾病造成的伤害。但到目前为止,科学家还没有成功地让它们发挥功效。如今,一个研究小组声称,他们已经促使这些细胞——被称为“米勒胶质细胞”——在老鼠的眼睛里再生了一种光受体细胞。根据科学家8月15日发表在英国《自然》杂志上的研究结果,这些新细胞可以探测到射入的光线,并与眼睛中的其他细胞结成网络向大脑传递信号,而这正是逆转某些遗传眼病和损伤的潜在步骤,这也为治疗视网膜色素


研究人员在老鼠视网膜上培育出新的感光细胞,能够将光转化为电信号。图片来源:Nathan Devery/Science Source

人眼中有一些细胞能够修复视力受损疾病造成的伤害。但到目前为止,科学家还没有成功地让它们发挥功效。如今,一个研究小组声称,他们已经促使这些细胞——被称为“米勒胶质细胞”——在老鼠的眼睛里再生了一种光受体细胞。根据科学家8月15日发表在英国《自然》杂志上的研究结果,这些新细胞可以探测到射入的光线,并与眼睛中的其他细胞结成网络向大脑传递信号,而这正是逆转某些遗传眼病和损伤的潜在步骤,这也为治疗视网膜色素变性等致盲疾病带来了新希望。但也有人对这一说法持怀疑态度,并认为这些信号可能来自于现有的光感细胞,而不是新生成的细胞。

美国马里兰州巴尔的摩市约翰斯·霍普金斯大学医学院神经学家Seth Blackshaw说:“没有人比我更希望这是真的,但我对这项研究怀有严重的担忧。”

论文作者、美国芒特西奈伊坎医学院神经及眼科学教授陈波介绍说,斑马鱼的视网膜具有自我修复功能,当视网膜受损后,其中的“米勒胶质细胞”可使视网膜的神经细胞再生,而哺乳动物的这种细胞却没有类似再生功能。虽然科学界已能通过损伤视网膜来激活哺乳动物的“米勒胶质细胞”,但此法对视网膜伤害较大,并不利于恢复视觉。

为此,研究人员在小鼠实验中利用基因转移的方法,促使“米勒胶质细胞”分裂并发育为可感光的视杆细胞。新发育的视杆细胞在结构上与天然视杆细胞没有差别,且形成了突触结构,使其能与视网膜内其他神经细胞交流。实验显示,这种方法可让先天失明的小鼠复明。

这项研究受到了美国国家眼科研究所的资助。该所视网膜神经科学项目主任托马斯·格林韦尔说,这是科学家首次在哺乳动物视网膜中,将“米勒胶质细胞”重编为能够发挥功能的视杆细胞。视杆细胞能让人们在暗光条件下看到东西,而且可能有助于保护视锥细胞,后者负责分辨颜色和提高视敏度。

陈波说,他们接下来计划借助体外培养实验,研究上述新法能否用于人的视网膜组织中。

“没有人能够像他们那样,制造出一种像光感受器一样的细胞。”得克萨斯州休斯顿大学眼科学院细胞和发育神经生物学家Deborah Otteson说。但她指出,即使是在重新生成最多新视杆细胞的老鼠体内,其密度也只是健康老鼠视网膜的0.2%。结果就是,被治疗的老鼠能够察觉到光,但它们无法辨认出形状或物体。

“他们已经破解了问题的第一部分,现在的问题是要把它放大。”Otteson说。她说,如果研究人员能够让“米勒胶质细胞”产生更多的感光细胞,那么这种方法有一天可能会让那些因为视网膜脱落或遗传障碍性视网膜炎而失去视杆细胞的人恢复一些视力。

肯塔基州路易斯维尔大学神经生物学家Maureen McCall称这项工作的“一大进步”在于恢复了视杆细胞,但强调研究团队仍需要证明视杆细胞的发育和功能在患病的眼睛中一切正常——这里的视网膜细胞可能不会正常连接和交互。

然而,Blackshaw看到了对新的研究结果的另一种解释:在盲鼠中,现有的杆状细胞在手术过程中被修复了,而这要么是因为它们接受了病毒携带的纠正基因,要么是因为“米勒胶质细胞”与它们分享了正确的基因。在这两种情况下,大脑的视觉信号都不是来自于新生成的杆状细胞,而是来自于现有感光细胞恢复的功能。他说,这项研究忽略了化学标记技术,它可以证明任何功能性杆状细胞都来自于“米勒胶质细胞”。

对此陈波表示,他和他的团队做了这样一个标记实验——尽管在论文中没有描述,而且他们已经通过其他几种方法彻底地证明了新杆状细胞的起源。他还引用了对照组实验,在实验中,该小组将校正基因转移到“米勒胶质细胞”上而没有重新编程。在这种情况下,大脑中并没有视觉信号,这意味着现有的杆状细胞没有被恢复。

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    2019-06-17 liye789132251
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    2019-07-01 sunylz
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    2018-08-23 zutt
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    2018-08-23 huangdf

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