Meyer Jason S, Katz Martin L, Kirk Mark D
University of Missouri, Division of Biological Sciences, 103 Lefevre Hall, Columbia MO 65211, USA.
Ann N Y Acad Sci. 2005 May;1049:135-45. doi: 10.1196/annals.1334.013.
Many systemic and eye-specific genetic disorders are accompanied by retinal degenerations that lead to blindness. In some of these diseases retinal degeneration occurs early in life and is quite rapid, whereas in other disorders, retinal degeneration starts later and progresses very slowly. At present, no therapies are available to patients for preventing or reversing the retinal degeneration that occurs in these diseases. Implantation of neural progenitor cells into the eye may be a means by which to retard or even reverse degeneration of the retina. To evaluate the potential of neural precursor cell implantation for treating retinal degenerative disorders, neuralized mouse embryonic stem cells from green fluorescent protein (GFP) transgenic mice were administered intravitreally to normal mice, mice with early retinal degeneration, and mice with slowly progressing retinal degeneration. In normal mice, the donor cells remained in the vitreous cavity and did not associate with the host retina. In mice with early retinal degeneration, implantation of the neural precursors was performed after the degeneration was almost complete. In these animals, the donor cells primarily associated closely with the inner surface of the retina, although a small fraction of donor cells did integrate into the host retina. Donor cells implanted in mice with slowly progressing retinal degeneration also associated with the inner retinal surface, but many more of the cells integrated into the retina. These findings indicate the importance of host tissue-donor cell interactions in determining the fate of implanted neural precursor cells. These interactions will be a major consideration when devising strategies for using cell implantation therapies for neurodegenerative disorders.
许多全身性和眼部特异性遗传疾病都伴有导致失明的视网膜变性。在其中一些疾病中，视网膜变性在生命早期就会发生且进展相当迅速，而在其他疾病中，视网膜变性则较晚开始且进展非常缓慢。目前，尚无针对这些疾病中发生的视网膜变性的预防或逆转疗法可供患者使用。将神经祖细胞植入眼内可能是延缓甚至逆转视网膜变性的一种方法。为了评估神经前体细胞植入治疗视网膜退行性疾病的潜力，将来自绿色荧光蛋白（GFP）转基因小鼠的神经化小鼠胚胎干细胞玻璃体内注射到正常小鼠、早期视网膜变性小鼠和缓慢进展性视网膜变性小鼠体内。在正常小鼠中，供体细胞留在玻璃体腔中，不与宿主视网膜发生关联。在早期视网膜变性小鼠中，在变性几乎完成后进行神经前体细胞植入。在这些动物中，供体细胞主要紧密地与视网膜内表面相关联，尽管一小部分供体细胞确实整合到了宿主视网膜中。植入缓慢进展性视网膜变性小鼠体内的供体细胞也与视网膜内表面相关联，但更多的细胞整合到了视网膜中。这些发现表明宿主组织 - 供体细胞相互作用在决定植入的神经前体细胞命运方面的重要性。在设计用于神经退行性疾病的细胞植入治疗策略时，这些相互作用将是一个主要考虑因素。
