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

bioRxiv [Preprint]. 2024 Nov 6:2024.11.04.621932. doi: 10.1101/2024.11.04.621932.

Abstract

Neuro- and retinal degenerative diseases rob millions of aging individuals of their independence. Researching these diseases in human tissue has been hindered by the immediate loss of electric activity in neurons after the circulation ceases. Recent studies indicate that limited neuronal activity can be revived postmortem, even in the retina. We capitalized on this discovery by successfully restoring and maintaining in vivo -like light responses in eyes recovered up to four hours and stored for up to 48 hours postmortem. This breakthrough significantly increases the availability of functionally viable human retinas for research. Our AI-based postmortem retinal imaging platform identifies retinal structures and allows us to compare light responses in the healthy central and peripheral retina with ex vivo electroretinography. We use this platform to measure the dark adaptation of human macular cones from controls and donors with age-related macular degeneration for the first time in the absence of the retinal pigment epithelium. We developed increased throughput technology and a model to simulate disease-associated acute ischemia-reperfusion. In this model, we demonstrate the protective or toxic effects of several drugs targeting oxidative stress or glutamate excitotoxicity.

Publication types

  • Preprint