Department of Ophthalmology, People's Hospital of Zhengzhou University; Department of Physiology, Basic College of Medicine, Zhengzhou University, Zhengzhou, China.
Department of Clinical Aerospace Medicine, Fourth Military Medical University, Xi'an, China.
Drug Deliv. 2021 Dec;28(1):218-228. doi: 10.1080/10717544.2020.1870584.
Retinal degeneration (RD) refers to a group of blinding retinopathies leading to the progressive photoreceptor demise and vision loss. Treatments against this debilitating disease are urgently needed. Intraocular delivery of exosomes represents an innovative therapeutic strategy against RD. In this study, we aimed to determine whether the subretinal delivery of RPE-derived exosomes (RPE-Exos) can prevent the photoreceptor death in RD. RD was induced in C57BL6 mice by MNU administration. These MNU administered mice received a single subretinal injection of RPE-Exos. Two weeks later, the RPE-Exos induced effects were evaluated via functional, morphological, and behavior examinations. Subretinal delivery of RPE-Exos efficiently ameliorates the visual function impairments, and alleviated the structural damages in the retina of MNU administered mice. Moreover, RPE-Exos exert beneficial effects on the electrical response of the inner retinal circuits. Treatment with RPE-Exos suppressed the expression levels of inflammatory factors, and mitigated the oxidative damage, indicating that subretinal delivery of RPE-Exos constructed a cytoprotective microenvironment in the retina of MNU administered mice. Our data suggest that RPE-Exos have therapeutic effects against the visual impairments and photoreceptor death. These findings will enrich our knowledge of RPE-Exos, and highlight the discovery of a promising medication for RD.
视网膜变性（RD）是一组致盲性视网膜病变，导致光感受器进行性死亡和视力丧失。针对这种使人衰弱的疾病，急需治疗方法。眼内递送达的外泌体是一种针对 RD 的创新治疗策略。在这项研究中，我们旨在确定视网膜色素上皮细胞衍生的外泌体（RPE-Exos）是否可以防止 RD 中的光感受器死亡。通过 MNU 给药在 C57BL6 小鼠中诱导 RD。这些接受 MNU 处理的小鼠接受单次视网膜下注射 RPE-Exos。两周后，通过功能、形态和行为检查评估 RPE-Exos 诱导的效果。视网膜下递送达 RPE-Exos 可有效改善视觉功能障碍，并减轻 MNU 处理小鼠视网膜的结构损伤。此外，RPE-Exos 对视网膜内电路的电反应产生有益影响。RPE-Exos 的治疗可抑制炎症因子的表达水平，并减轻氧化损伤，表明 RPE-Exos 在 MNU 处理的小鼠视网膜中构建了一种细胞保护的微环境。我们的数据表明，RPE-Exos 对视觉障碍和光感受器死亡具有治疗作用。这些发现将丰富我们对 RPE-Exos 的认识，并强调发现一种有前途的 RD 药物。
