University of Alabama at Birmingham, Department of Ophthalmology, Birmingham, AL 35294-0009, USA.
Expert Opin Biol Ther. 2010 Aug;10(8):1227-39. doi: 10.1517/14712598.2010.495218.
Retinal degenerations cause blindness. One potential therapy is cell replacement. Because the human retina lacks regeneration capacity, much attention has been directed towards searching for cells that can differentiate into retinal neurons.
We discuss the possibility of using transcription factor genes to channel retinal pigment epithelial (RPE) cells' capabilities of proliferation and plasticity towards the production of retinal neurons.
Experiments with chick embryos show that RPE cells - in the eye, in explant, or in a dissociated cell culture - can give rise to cells resembling retinal neurons when reprogrammed with regulatory genes involved in retinal neurogenesis. Depending on the regulatory gene used, reprogramming generates cells exhibiting traits of photoreceptor cells, amacrine cells and/or young ganglion neurons.
Gene-directed reprogramming of chick RPE can efficiently generate cells that exhibit traits of retinal neurons. Remaining to be addressed is the question of whether the results from chicks apply to mammals. Since the RPE is located adjacent to the neural retina, RPE reprogramming, if successful in mammals, may offer an approach to repopulate the neural retina without involving cell transplantation.
视网膜变性导致失明。一种潜在的治疗方法是细胞替代。由于人类视网膜缺乏再生能力，因此人们非常关注寻找可以分化为视网膜神经元的细胞。
我们讨论了使用转录因子基因将视网膜色素上皮 (RPE) 细胞的增殖和可塑性能力引导为产生视网膜神经元的可能性。
鸡胚实验表明，当用参与视网膜神经发生的调节基因对 RPE 细胞进行重编程时，在眼睛、外植体或分离的细胞培养物中的 RPE 细胞可以产生类似于视网膜神经元的细胞。根据使用的调节基因，重编程产生表现出光感受器细胞、无长突细胞和/或年轻节细胞特征的细胞。
基因定向重编程鸡 RPE 可以有效地产生表现出视网膜神经元特征的细胞。仍有待解决的问题是，鸡的结果是否适用于哺乳动物。由于 RPE 位于神经视网膜旁边，如果在哺乳动物中成功进行 RPE 重编程，可能会提供一种无需细胞移植即可重新 populate 神经视网膜的方法。
