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bioRxiv · 10.1101/2024.11.04.621932

Restoring and sustaining human postmortem retinal light responses with scalable methods for testing degenerative disease therapies

Becker, S.·Allen, J.·L'Ecuyer Morison, Z.·Saeid, S.·Koskelainen, A.·Vinberg, F.
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Abstract

Neuro- and retinal degenerative diseases, including Alzheimers, age-related macular degeneration, stroke, and central retinal artery occlusion, rob millions of their independence. Studying these diseases in human retinas has been hindered by the immediate loss of neuronal activity postmortem. While recent studies restored limited activity in postmortem CNS tissues, synchronized neuronal transmission >30 minutes postmortem remained elusive. Our study overcomes this barrier by reviving and sustaining light signal transmission in human retinas recovered up to four hours and stored 48 hours postmortem. We also establish infrared-based ex vivo imaging for precise sampling, a closed perfusion system for drug testing, and an ex vivo ischemia-reperfusion model in mouse and human retina. This platform enables testing of neuroprotective and neurotoxic effects of drugs targeting oxidative stress and glutamate excitotoxicity. Our advances question the irreversibility of ischemic injury, support preclinical vision restoration studies, offer new insights into treating ischemic CNS injuries, and pave the way for transplantation of human donor eyes. TeaserReviving light signaling in postmortem human retinas challenges the irreversibility of ischemic injury and advances research to restore vision.

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Becker, S., Allen, J., L'Ecuyer Morison, Z., Saeid, S., Koskelainen, A., Vinberg, F.. 2024-11-06. Restoring and sustaining human postmortem retinal light responses with scalable methods for testing degenerative disease therapies. https://doi.org/10.1101/2024.11.04.621932

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