SN ONGC Department of Genetics and Molecular Biology, Vision Research Foundation, Chennai, 600 006, India.
Department of Human Genetics and Molecular Biology, Bharathiar University, Coimbatore, 641 046, India.
Int Ophthalmol. 2022 Sep;42(9):2949-2964. doi: 10.1007/s10792-022-02267-9. Epub 2022 Mar 31.
Optic neuropathy has become a new typical syndromic multi-system disease that leads to optic atrophy. This review discusses potential treatments and advances of Leber's hereditary optic neuropathy (LHON), a sporadic genetic disorder. LHON is caused due to slight mutations in mitochondria leading to mitochondrial dysfunction, causing vision loss. There are no current significant treatments that have been proven to work for LHON.
However, extensive review was carried out on capable studies that have shown potential treatment sensory systems and are being evaluated currently. Some of these studies are in clinical trials, whereas other ones are still being planned. Here, we focus more on treatment based on mesenchymal stem cells-mediated mitochondrial transfer via various techniques. We discuss different mitochondrial transfer modes and possible ways to understand the mitochondria transfer technique's phenotypic characteristics.
It is clearly understood that transfer of healthy mitochondria from MSC to target cell would regulate the range of reactive oxygen species and ATP'S, which are majorly responsible for mutation upon irregulating. Therefore, mitochondrial transfer is suggested and discussed in this review with various aspects. The graphical abstract represents different means of mitochondrial transport like (a) Tunnelling nanotubules, (b) Extracellular vesicles, (c) Cell fusion and (d) Gap junctions. In (a) Tunnelling nanotubules, the signalling pathways TNF- α/TNF αip2 and NFkB/TNF αep2 are responsible for forming tunnels. Also, Miro protein acts as cargo for the transport of mitochondria with myosin's help in the presence of RhoGTPases [35]. In (b) Extracellular vesicles, the RhoA ARF6 contributes to Actin/Cytoskeletal rearrangement leading to the shedding of microvesicles. Coming to (c) Cell fusion when there is a high amount of ATP, the cells tend to fuse when in close proximity leading to the transfer of mitochondria via EFF-1/HAP2 [48]. In (d) Gap Junctions, Connexin43 is responsible for the intracellular channel in the presence of more ATP [86].
视神经病变已成为一种新的典型多系统疾病，可导致视神经萎缩。本综述讨论了莱伯遗传性视神经病变（LHON）的潜在治疗方法和进展，LHON 是一种散发性遗传疾病。LHON 是由于线粒体的微小突变导致线粒体功能障碍引起的，从而导致视力丧失。目前尚无经过证实对 LHON 有效的显著治疗方法。
然而，我们对有潜力的研究进行了广泛的综述，这些研究表明了一些潜在的治疗感觉系统，并正在进行评估。其中一些研究正在进行临床试验，而其他研究仍在计划中。在这里，我们更关注基于间充质干细胞介导的通过各种技术进行线粒体转移的治疗方法。我们讨论了不同的线粒体转移模式和理解线粒体转移技术表型特征的可能途径。
显然，从 MSC 向靶细胞转移健康的线粒体可以调节活性氧和 ATP 的范围，这是突变的主要原因。因此，线粒体转移在本综述中通过各种方面进行了建议和讨论。图形摘要代表了不同的线粒体运输方式，如（a）隧穿纳米管，（b）细胞外囊泡，（c）细胞融合和（d）间隙连接。在（a）隧穿纳米管中，信号通路 TNF-α/TNFαip2 和 NFkB/TNFαep2 负责形成隧道。此外，Miro 蛋白在 RhoGTPases 的帮助下，通过肌球蛋白的作用作为线粒体运输的货物发挥作用 [35]。在（b）细胞外囊泡中，RhoA ARF6 有助于肌动蛋白/细胞骨架重排，导致微泡脱落。在（c）细胞融合中，当存在大量 ATP 时，细胞趋于融合，当它们靠近时，通过 EFF-1/HAP2 转移线粒体 [48]。在（d）间隙连接中，Connexin43 在存在更多 ATP 的情况下负责细胞内通道 [86]。
