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世界生命科学前沿动态周报（八十五）
干细胞方法治疗失明成功用于老鼠
科技日报Science Daily 2013年1月7日：牛津大学纳菲尔德临床神经科学系的教授Robert MacLaren和新加坡国立大学医院的眼科医生Mandeep Singh研究发现，将发育中的细胞移植入失明老鼠的眼睛后，能够重建其视网膜的整个光敏层。《美国国家科学院院刊》在线发表了他们的相关研究结果。
研究人员称这个方法可以帮助治疗色素性视网膜炎患者，这类患者因视网膜的光敏细胞逐渐死亡导致渐进性失明。他们用最近似的失明老鼠模型做实验，两周后发现将发育细胞移植入眼后在视网膜上重建了整个光敏层，且老鼠可以看见东西了。他们使用的是老鼠发育中的视网膜细胞初期的前体细胞。瞳孔收缩实验发现12只老鼠中有10只老鼠对光的瞳孔收缩反应提高，表明老鼠的视网膜再次有了光感，且经视神经盘传至了大脑。
Dr. Singh说，“我们发现如果将足够数量的细胞移植在一起，不仅能产生光敏性，而且还能再生出产生视力所需的连接。MacLaren称他们想使用iPSCs来进行研究，希望可以实现细胞疗法治疗人类失明。这些来自患者体内的细胞如皮肤或血液细胞产生的干细胞可以直接形成视网膜细胞的前体细胞。他还称这是前人实现的结果，将来在患者上的应用如同探囊取物。下一步的目标是在病人体内找到可靠的细胞来源以便提供细胞移植所需的干细胞。
点评: 用iPSCs来进行色素性视网膜炎研究目前只是实现了此类老鼠再次获得光感，但如何解决再生出产生视力所需的连接仍是主要的难题。
相关文献：
Reversal of end-stage retinal degeneration and restoration of visual function by transplantation
Author: Mandeep S. Singha, Peter Charbel Issaa, Rachel Butlera, Chris Martinb, Daniel M. Lipinskia, Sumathi Sekarana, Alun R. Barnarda, and Robert E. MacLarena,c,d,1
Edited by Constance L. Cepko, Harvard Medical School and Howard Hughes Medical Institute, Boston, MA, and approved December 7, 2012 (received for review November 24, 2011)
Abstract
One strategy to restore vision in retinitis pigmentosa and age-related macular degeneration is cell replacement. Typically, patients lose vision when the outer retinal photoreceptor layer is lost, and so the therapeutic goal would be to restore vision at this stage of disease. It is not currently known if a degenerate retina lacking the outer nuclear layer of photoreceptor cells would allow the survival, maturation, and reconnection of replacement photoreceptors, as prior studies used hosts with a preexisting outer nuclear layer at the time of treatment. Here, using a murine model of severe human retinitis pigmentosa at a stage when no host rod cells remain, we show that transplanted rod precursors can reform an anatomically distinct and appropriately polarized outer nuclear layer. A trilaminar organization was returned to rd1 hosts that had only two retinal layers before treatment. The newly introduced precursors were able to resume their developmental program in the degenerate host niche to become mature rods with light-sensitive outer segments, reconnecting with host neurons downstream. Visual function, assayed in the same animals before and after transplantation, was restored in animals with zero rod function at baseline. These observations suggest that a cell therapy approach may reconstitute a light-sensitive cell layer de novo and hence repair a structurally damaged visual circuit. Rather than placing discrete photoreceptors among preexisting host outer retinal cells, total photoreceptor layer reconstruction may provide a clinically relevant model to investigate cell-based strategies for retinal repair.