By Pooja Toshniwal PahariaReviewed by Lauren HardakerFeb 5 2026Restored light responses in donated human eyes show that retinal neurons can recover after oxygen loss, opening new paths to protect and restore vision.
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A recent Science Advances study reveals that human retinas can recover measurable electrical responses to light in postmortem tissue, challenging long-standing views of irreversible ischemic injury.
By restoring retinal function in select donor eyes up to approximately four hours postmortem and maintaining functional light-evoked signaling ex vivo, researchers created a powerful human neural ischemia–reperfusion (hypoxia–reoxygenation) model of retinal injury. The platform combines infrared imaging, closed-loop perfusion, and ischemia–reperfusion paradigms to accelerate the evaluation of neuroprotective agents and vision-restoring therapies.
Neurodegenerative and retinal ischemic disorders, including stroke and central retinal artery occlusion (CRAO), remain major causes of vision loss and neurological disability worldwide, with few effective treatments. Progress has long been limited by the assumption that neuronal function in the human central nervous system (CNS), encompassing the retina, irreversibly declines shortly after circulatory death.
While recent work has shown partial metabolic or cellular recovery in postmortem CNS tissue, the ability to restore and sustain coordinated functional neural signaling has yet to be achieved. Overcoming this limitation is essential for developing human-relevant neural hypoxia–reperfusion models and accelerating translation of neuroprotective and vision-restoring therapies.
Postmortem Human Retinas Revived Using Controlled Oxygen Delivery
In the present study, researchers investigated whether retinal function can be recovered and maintained after prolonged ischemia using postmortem human and mouse retinas. To do so, they obtained human donor eyes without known retinal disease from organ and research donors, with postmortem intervals ranging from under one hour to up to five hours, depending on donor type and tissue-handling protocols.
After removal of the anterior segment and vitreous, the researchers performed infrared optical coherence tomography (OCT) followed by fundus imaging ex vivo to visualize retinal anatomy and locate the fovea. A custom optical adapter and deep learning–based algorithms enabled precise sampling of macular and peripheral regions.
The team collected retinal tissue using biopsy punches and incubated them in oxygenated bicarbonate-buffered Ames’ medium to restore metabolic activity. They exposed the samples to hypoxia followed by controlled reoxygenation to model neural oxygen deprivation and reperfusion. They performed ex vivo electroretinography (ERG) to evaluate retinal function by quantifying photoreceptor activity and ON-bipolar signaling. Subsequently, the researchers applied selective pharmacological blockers to isolate neuronal pathways and examine recovery dynamics.
The authors conducted parallel experiments in wild-type and genetically modified mice to assess cell-type–specific vulnerability to hypoxia. They analyzed multi-electrode array recordings to measure retinal ganglion cell activity. A closed-loop perfusion system recirculated small volumes of perfusate to minimize tissue and drug use while enabling extended recordings.
Lastly, the researchers performed immunohistochemistry (IHC) and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assays to assess cellular stress, inflammation, and apoptosis. They tested several neuroprotective agents that target oxidative stress and excitotoxicity to preserve or restore retinal light responses. These agents included dimethyl malonate, apocynin, and the N-methyl-D-aspartate (NMDA) receptor antagonists MK-801 and memantine.
Photoreceptors Resist Hypoxia While Inner Retina Recovers Variably
The researchers showed that light-evoked retinal responses can be preserved in intact human posterior eyes for nearly two days after death, provided the retina remains attached to the retinal pigment epithelium (RPE) and contamination is avoided. Although early experiments failed to recover ON-bipolar cell responses in the macular region, optimized protocols preserved central retinal light signaling in some samples for at least 24 hours.
Substantial variability was observed between donor eyes, and only a subset exhibited robust inner retinal recovery. In these cases, inner retinal responses after a 24-hour period matched or exceeded those of freshly isolated tissue, indicating partial functional recovery following ischemic injury rather than uniform preservation.
ERG analyses revealed that photoreceptors were more resistant to hypoxia than ON-bipolar cells, retaining over 50% of their light responses for at least 30 minutes. One hour of hypoxia followed by overnight incubation fully restored photoreceptor and ON-bipolar cell function, whereas recovery after three hours was incomplete. Histological analyses showed limited cell death despite marked functional impairment, suggesting largely reversible signaling deficits rather than widespread neuronal loss.
The platform enabled extended recordings, with peripheral human retinas maintaining stable rod photoreceptor responses for over 12 hours under closed-loop perfusion. Light-evoked activity from multiple retinal ganglion cell types was preserved for up to 24 hours after optic nerve transection in at least one donor eye, although the authors note that the long-term consequences of axotomy on retinal ganglion cell survival and functional integrity remain unclear. Infrared OCT combined with deep learning enabled precise foveal localization.
Pharmacological studies showed that limiting reactive oxygen species (ROS) partially protected photoreceptor function during ischemia–reperfusion. Apocynin improved recovery after prolonged hypoxia, while dimethyl malonate was most effective when applied during hypoxia or just before reoxygenation. In contrast, combined ROS inhibition reduced efficacy, and ON-bipolar cell responses remained largely unaffected, highlighting cell-type–specific injury and repair mechanisms.
Retinal Ischemic Injury Shown To Be Time-Dependent and Reversible
The study findings demonstrate that ischemic injury in the human retina is not invariably irreversible and that retinal neurons can recover light responses when oxygenation is restored within a defined, time-dependent therapeutic window. Early oxygen delivery via vitreous perfusion, combined with targeted neuroprotective approaches, may preserve retinal neural signaling capacity until circulation is reestablished.
The findings highlight new therapeutic opportunities for acute retinal ischemia, including CRAO, for which effective treatments are limited. The ischemia–reperfusion platform also offers a human neural tissue–based experimental system for studying neuronal recovery following hypoxic injury, with potential implications for stroke, cardiac arrest, and future vision restoration.
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Journal Reference
Becker, S. et al. (2026). Healing of ischemic injury in the retina. Science Advances, 12(4), eadx7204. DOI: 10.1126/sciadv.adx7204. https://www.science.org/doi/10.1126/sciadv.adx7204
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