Borsch O, Santos-Ferreira T, Ader M
Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden.
Klin Monbl Augenheilkd. 2017 Mar;234(3):343-353. doi: 10.1055/s-0043-104421. Epub 2017 Mar 29.
Vision impairment and blindness due to photoreceptor loss represents one of the major causes for disability in industrialized societies. Whereas rod photoreceptors allow vision under dim light conditions, cone photoreceptors provide high-acuity vision in daylight conditions and color detection. Several therapeutic strategies are currently developed to repair vision loss, including cell-based interventions. Within the last decade, major progress regarding the replacement of photoreceptors by transplantation has been made in pre-clinical animal models. This includes defining the necessary conditions, like the optimal ontogenetic stage of transplantable donor photoreceptors, cell-specific enrichment procedures and robust transplantation technologies. Moreover, first studies provided evidence for functional improvements by photoreceptor transplantation in mouse models of retinal dysfunction. Furthermore, advances in cell culture technology were made by introducing methods to generate photoreceptor-containing retinal organoids, derived from pluripotent stem cells, that provide theoretically unlimited sources for the production of photoreceptor transplants. Interestingly, the recently identified transfer of cytoplasmic material between donor and host photoreceptors might represent an additional treatment option for cell transplantation approaches. Within this review, we focus on the main developments within the photoreceptor transplantation field and discuss important achievements, challenges and hurdles to develop photoreceptor transplantation towards clinical applications.
在工业化社会中,因光感受器丧失导致的视力损害和失明是致残的主要原因之一。视杆光感受器使人们能够在暗光条件下视物,而视锥光感受器则在日光条件下提供高敏锐度视觉并进行颜色检测。目前正在开发多种治疗策略来修复视力丧失,包括基于细胞的干预措施。在过去十年中,临床前动物模型在通过移植替代光感受器方面取得了重大进展。这包括确定必要条件,如可移植供体光感受器的最佳个体发育阶段、细胞特异性富集程序和强大的移植技术。此外,首批研究为视网膜功能障碍小鼠模型中光感受器移植带来的功能改善提供了证据。此外,通过引入从多能干细胞衍生出含光感受器的视网膜类器官的方法,细胞培养技术取得了进展,这为生产光感受器移植体提供了理论上无限的来源。有趣的是,最近发现的供体和宿主光感受器之间的细胞质物质转移可能为细胞移植方法提供了另一种治疗选择。在本综述中,我们重点关注光感受器移植领域的主要进展,并讨论将光感受器移植发展到临床应用的重要成果、挑战和障碍。