First intravitreal mitochondrial transplantation for bilateral vision loss

<title>Abstract</title> <p>Mitochondrial transplantation delivers viable, respiration-competent mitochondria into tissue whose own mitochondria have been damaged. It has been performed in the human heart and brain, but not in the eye, and no dose, safety profile or delivery experience existed for that compartment. Retinal ganglion cells depend heavily on oxidative phosphorylation, and in rodents mitochondria injected into the vitreous are taken up by these cells and improve survival after optic nerve injury. Here we show that fresh autologous mitochondria, isolated at the point of care, can be injected into the human vitreous without ocular or systemic toxicity. A 26-year-old woman with bilateral optic neuropathy fixed for three months after prolonged cerebral hypoperfusion received one injection into each eye, 24 hours apart, under emergency expanded access. Neither eye developed intraocular inflammation, and automated pupillary reactivity, absent across 45 readings over the preceding 71 days, returned in each eye within days of its own injection, transiently and without measurable acuity change.</p>