Institute of Ophthalmology and Visual Science, Rutgers-New Jersey Medical School, Rutgers University, Newark, New Jersey, USA.
Department of Pharmacology, Physiology, and Neuroscience, Rutgers-New Jersey Medical School, Newark, New Jersey, USA.
Stem Cells Transl Med. 2019 May;8(5):466-477. doi: 10.1002/sctm.18-0282. Epub 2019 Feb 12.
Retinal cell therapy can have the objectives of rescue (i.e., modulation of metabolic abnormalities primarily for sight preservation) as well as replacement (i.e., replace cells lost due to injury or disease for sight restoration as well as preservation). The first clinical trials of retinal pigment epithelium (RPE) transplantation for vision-threatening complications of age-related macular degeneration (AMD) have begun with some preliminary signs of success (e.g., improvement in vision in some patients, anatomic evidence of transplant-host integration with some evidence of host photoreceptor recovery, long-term survival of autologous induced pluripotent stem cell-derived RPE transplants without immune suppression) as well as limitations (e.g., limited RPE suspension survival in the AMD eye, limited tolerance for long-term systemic immune suppression in elderly patients, suggestion of uncontrolled cell proliferation in the vitreous cavity). RPE survival on aged and AMD Bruch's membrane can be improved with chemical treatment, which may enhance the efficacy of RPE suspension transplants in AMD patients. Retinal detachment, currently used to deliver transplanted RPE cells to the subretinal space, induces disjunction of the first synapse in the visual pathway: the photoreceptor-bipolar synapse. This synaptic change occurs even in areas of attached retina near the locus of detachment. Synaptic disjunction and photoreceptor apoptosis associated with retinal detachment can be reduced with Rho kinase inhibitors. Addition of Rho kinase inhibitors may improve retinal function and photoreceptor survival after subretinal delivery of cells either in suspension or on scaffolds.
视网膜细胞疗法的目标可以是挽救（即主要调节代谢异常以维持视力），也可以是替代（即因损伤或疾病而丧失的细胞，以恢复视力并维持）。已经开始了针对与年龄相关性黄斑变性（AMD）相关的威胁视力的并发症的视网膜色素上皮（RPE）移植的首次临床试验，有一些初步成功的迹象（例如，一些患者的视力有所改善，移植宿主整合的解剖学证据，以及一些宿主光感受器恢复的证据，自体诱导多能干细胞衍生的 RPE 移植在没有免疫抑制的情况下长期存活），但也存在一些局限性（例如，AMD 眼中 RPE 悬浮液的存活有限，老年患者长期耐受全身免疫抑制的能力有限，玻璃体内无控制的细胞增殖的提示）。化学处理可以改善老化和 AMD 布鲁赫膜上的 RPE 存活，这可能会提高 AMD 患者 RPE 悬浮液移植的疗效。视网膜脱离目前用于将移植的 RPE 细胞递送至视网膜下腔，会导致视觉通路中第一个突触的分离：光感受器-双极突触。即使在脱离部位附近的附着视网膜区域，也会发生这种突触变化。用 Rho 激酶抑制剂可以减少与视网膜脱离相关的突触分离和光感受器凋亡。在用悬浮液或支架进行细胞的视网膜下递送后，添加 Rho 激酶抑制剂可能会改善视网膜功能和光感受器的存活。
