Mesenchymal stem cells (MSCs) in Leber's hereditary optic neuropathy (LHON): a potential therapeutic approach for future

Int Ophthalmol. 2022 Sep;42(9):2949-2964. doi: 10.1007/s10792-022-02267-9. Epub 2022 Mar 31.


Background: 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.

Methods: 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.

Conclusion: 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].

Keywords: Gene therapy; Leber’s hereditary optic neuropathy; Mesenchymal stem cells; Micro-vesicles-mediated transfer; Mitochondrial transfer; Tunnelling nanotubes.

Publication types

  • Review

MeSH terms

  • Adenosine Triphosphate
  • DNA, Mitochondrial
  • Humans
  • Mesenchymal Stem Cells*
  • Mitochondria
  • Mutation
  • Optic Atrophy, Hereditary, Leber*
  • Reactive Oxygen Species


  • DNA, Mitochondrial
  • Reactive Oxygen Species
  • Adenosine Triphosphate