Department of Ophthalmology, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
Ocular and Stem Cell Translational Research Section, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Adv Exp Med Biol. 2021;1256:265-293. doi: 10.1007/978-3-030-66014-7_11.
Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. The pathogenesis of AMD involves dysfunction and loss of the retinal pigment epithelium (RPE), a monolayer of cells that provide nourishment and functional support for the overlying photoreceptors. RPE cells in mammals are not known to divide, renew or regenerate in vivo, and in advanced AMD, RPE loss leads to degeneration of the photoreceptors and impairment of vision. One possible therapeutic approach would be to support and replace the failing RPE cells of affected patients, and indeed moderate success of surgical procedures in which relatively healthy autologous RPE from the peripheral retina of the same eye was transplanted under the retina in the macular area suggested that RPE replacement could be a means to attenuate photoreceptor cell loss. This prompted exploration of the possibility to use pluripotent stem cells (PSCs) as a potential source for "healthy and young" RPE cells for such cell-based therapy of AMD. Various approaches ranging from the use of allogeneic embryonic stem cells to autologous induced pluripotent stem cells are now being tested within early clinical trials. Such PSC-derived RPE cells are either injected into the subretinal space as a suspension, or transplanted as a monolayer patch upon scaffold support. Although most of these approaches are at early clinical stages, safety of the RPE product has been demonstrated by several of these studies. Here, we review the concept of cell-based therapy of AMD and provide an update on current progress in the field of RPE transplantation.
年龄相关性黄斑变性（AMD）是全球范围内导致失明的主要原因之一。AMD 的发病机制涉及视网膜色素上皮（RPE）的功能障碍和丧失，RPE 是一层为其上的感光细胞提供营养和功能支持的细胞。哺乳动物的 RPE 细胞已知不会在体内分裂、更新或再生，在晚期 AMD 中，RPE 的丧失导致感光细胞变性和视力损害。一种可能的治疗方法是支持和替代受影响患者的衰竭的 RPE 细胞，事实上，在相对健康的同种异体 RPE 从同一眼的周边视网膜下移植到黄斑区视网膜下的手术中取得了一定的成功，这表明 RPE 替代可能是减轻感光细胞丧失的一种手段。这促使人们探索使用多能干细胞（PSCs）作为“健康和年轻”的 RPE 细胞的潜在来源，用于 AMD 的基于细胞的治疗。目前正在早期临床试验中测试各种方法，包括使用异体胚胎干细胞和自体诱导多能干细胞。这些源自 PSC 的 RPE 细胞要么作为悬浮液注入到视网膜下腔，要么在支架支持下作为单层贴片进行移植。尽管这些方法大多处于早期临床阶段，但这些研究中的几项已经证明了 RPE 产物的安全性。在这里，我们回顾了 AMD 的基于细胞的治疗概念，并提供了 RPE 移植领域当前进展的最新情况。
