Chow Lorraine L C, Mead Ben
School of Optometry and Vision Sciences, Cardiff University, Cardiff, UK.
Neural Regen Res. 2023 Sep;18(9):1876-1880. doi: 10.4103/1673-5374.367835.
Age-related macular degeneration is a major global cause of central visual impairment and severe vision loss. With an aging population, the already immense economic burden of costly anti-vascular endothelial growth factor treatment is likely to increase. In addition, current conventional treatment is only available for the late neovascular stage of age-related macular degeneration, and injections can come with potentially devastating complications, introducing the need for more economical and risk-free treatment. In recent years, exosomes, which are nano-sized extracellular vesicles of an endocytic origin, have shown immense potential as diagnostic biomarkers and in the therapeutic application, as they are bestowed with characteristics including an expansive cargo that closely resembles their parent cell and exceptional ability of intercellular communication and targeting neighboring cells. Exosomes are currently undergoing clinical trials for various conditions such as type 1 diabetes and autoimmune diseases; however, exosomes as a potential therapy for several retinal diseases have just begun to undergo scrutinizing investigation with little literature on age-related macular degeneration specifically. This article will focus on the limited literature available on exosome transplantation treatment in age-related macular degeneration animal models and in vitro cell cultures, as well as briefly identify future research directions. Current literature on exosome therapy using age-related macular degeneration rodent models includes laser retinal injury, N-methyl-N-nitrosourea, and royal college of surgeon models, which mimic inflammatory and degenerative aspects of age-related macular degeneration. These have shown promising results in preserving retinal function and morphology, as well as protecting photoreceptors from apoptosis. Exosomes from their respective cellular origins may also act by regulating the expression of various inflammatory cytokines, mRNAs, and proteins involved in photoreceptor degeneration pathways to exert a therapeutic effect. Various findings have also opened exciting prospects for the involvement of cargo components in remedial effects on the damaged macula or retina.
年龄相关性黄斑变性是导致全球中心视力损害和严重视力丧失的主要原因。随着人口老龄化,昂贵的抗血管内皮生长因子治疗本已巨大的经济负担可能会增加。此外,目前的传统治疗仅适用于年龄相关性黄斑变性的晚期新生血管阶段,且注射可能会带来潜在的毁灭性并发症,因此需要更经济且无风险的治疗方法。近年来,外泌体作为一种内吞起源的纳米级细胞外囊泡,已显示出作为诊断生物标志物和治疗应用的巨大潜力,因为它们具有多种特性,包括含有与母细胞极为相似的丰富成分,以及卓越的细胞间通讯和靶向邻近细胞的能力。目前外泌体正在针对1型糖尿病和自身免疫性疾病等多种病症进行临床试验;然而,外泌体作为几种视网膜疾病的潜在治疗方法才刚刚开始受到仔细研究,关于年龄相关性黄斑变性的文献尤其少。本文将聚焦于年龄相关性黄斑变性动物模型和体外细胞培养中外泌体移植治疗的有限文献,并简要确定未来的研究方向。目前关于使用年龄相关性黄斑变性啮齿动物模型进行外泌体治疗的文献包括激光视网膜损伤、N-甲基-N-亚硝基脲和皇家外科学院模型,这些模型模拟了年龄相关性黄斑变性的炎症和退行性方面。这些研究在保留视网膜功能和形态以及保护光感受器免于凋亡方面显示出了有前景的结果。来自各自细胞来源的外泌体也可能通过调节参与光感受器变性途径的各种炎性细胞因子、mRNA和蛋白质的表达来发挥治疗作用。各种研究结果也为货物成分参与对受损黄斑或视网膜的修复作用开辟了令人兴奋的前景。