Journal
NATURE
Volume 606, Issue 7913, Pages 351-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41586-022-04709-x
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Funding
- National Institutes of Health [P30 EY014800, R01 EY015128, R01 EY028927, R01: CA236352, R01: DK115214, R01: DK118278]
- Research to Prevent Blindness
- NIH/NCATS grant [UL1 TR002550]
- NIH [EY031706]
- Daro Foundation
- A. C. Israel Foundation
- Warren Family Foundation
- Renaissance Charitable Foundation
- Rancho Santa Fe Foundation
- Money Arenz Foundation
- Considine Foundation
- Fonseca Foundation
- Pfeiffer Foundation
- Mericos Eye Institute
- Thomas and Audrey Pine Foundation
- Research to Prevent Blindness/Dr. H. James and Carole Free Career Development Award
- Diabetes Research Connection
- International Retinal Research Foundation
- ARVO Foundation for Eye Research EyeFind research grant
- National Science Foundation [2014862]
- Department of Defense [W81XWH1810645]
- Wu-Tsai Human Performance Alliance
- Joe and Clara Tsai Foundation
- Velux Stiftung
- Div Of Biological Infrastructure
- Direct For Biological Sciences [2014862] Funding Source: National Science Foundation
- U.S. Department of Defense (DOD) [W81XWH1810645] Funding Source: U.S. Department of Defense (DOD)
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In this study, the researchers used the retina as a model to investigate the process of death and neuronal revival in the central nervous system. They found that under certain conditions, postmortem mouse and human retinas can revive synchronous in vivo-like trans-synaptic transmission. They also identified modifiable factors that drive reversible and irreversible loss of light signalling after death.
Death is defined as the irreversible cessation of circulatory, respiratory or brain activity. Many peripheral human organs can be transplanted from deceased donors using protocols to optimize viability. However, tissues from the central nervous system rapidly lose viability after circulation ceases(1,2), impeding their potential for transplantation. The time course and mechanisms causing neuronal death and the potential for revival remain poorly defined. Here, using the retina as a model of the central nervous system, we systemically examine the kinetics of death and neuronal revival. We demonstrate the swift decline of neuronal signalling and identify conditions for reviving synchronous in vivo-like trans-synaptic transmission in postmortem mouse and human retina. We measure light-evoked responses in human macular photoreceptors in eyes removed up to 5 h after death and identify modifiable factors that drive reversible and irreversible loss of light signalling after death. Finally, we quantify the rate-limiting deactivation reaction of phototransduction, a model G protein signalling cascade, in peripheral and macular human and macaque retina. Our approach will have broad applications and impact by enabling transformative studies in the human central nervous system, raising questions about the irreversibility of neuronal cell death, and providing new avenues for visual rehabilitation.
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