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WGC-2021

Editors Selection IGR 21-1

Medical Treatment: Mitotherapy in Glaucoma

Jonathan Crowston

Comment by Jonathan Crowston on:

84974 Neuroprotection from optic nerve injury and modulation of oxidative metabolism by transplantation of active mitochondria to the retina, Nascimento-Dos-Santos G; Nascimento-Dos-Santos G; de-Souza-Ferreira E; Lani R et al., Biochimica et Biophysica Acta - Molecular Basis of Disease, 2020; 1866: 165686

See also comment(s) by Keith Martin


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The authors performed an innovative set of experiments where mitochondria isolated from the livers of young Lister Hooded rats were injected intravitreally with the aim of providing neuroprotection and axonal regeneration following optic nerve crush in similar aged rats. Lysed mitochondria or saline were used for controls. Mitochondrial were seen to integrate into host axons at 24 hours and led to a short-term but not sustained alteration in respiratory capacity. Injection of intact liver mitochondria afforded a modest increase in GC survival after optic nerve crush and intriguingly lysed-mitochondria but not intact-mitochondrial promoted axonal regeneration. Also surprising was the discovery that injected mitochondria increased a-wave (outer retina) and b-waves (mid-retina) of a full-field ERG. Inner retina recordings were unfortunately not performed and insufficient data was provided in the main text to examine these changes in more detail and it was not evident whether transplanted mitochondria integrated into all the retinal layers.

Accumulating evidence . . . is pointing to mitochondrial dysfunction playing a role in glaucoma pathogenesis.

Accumulating evidence from our laboratory and others is pointing to mitochondrial dysfunction playing a role in glaucoma pathogenesis. Mitochondria can be easily isolated and the vitreous chamber is an ideal reservoir for biologic therapies. One aspect that needs to be borne in mind is that the native mitochondria remain in the host RGCs and it is not clear how these will integrate with transplanted mitochondria. As the majority of mitochondrial proteins are derived from nuclear not mitochondria DNA, transplantation will lead to a potential mismatch between transplanted mtDNA and host nuclear DNA. This, at least theoretically, has potential for inciting variations in the OXPHOS complex subunits and their assembly, which in the longer term could lead to dysfunction or incite inflammation.



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WGC-2021