Treating retinal degenerative diseases by bringing human retinas back to life
Jed Boye | | 3 min read | News
Death has always appeared to draw a line in the sand – a clear point of no return. But the results of a new study in which, for the first time, researchers have revived retinal neurons from a human eye hours after death indicate that the end of life may not necessarily equal the end of sight.
So how does one decide to begin the process of combating death? Frans Vinberg, Assistant Professor of Ophthalmology and Visual Sciences at the University of Utah and corresponding author of the paper, explains, “Around 2014, I realized that there was not much information regarding the detailed light signaling pathways of the human macula and how these were affected in diseases such as AMD. The actual work with human donor eyes became a possibility after I met Anne Hanneken [Associate Professor in the Department of Molecular Medicine at The Scripps Research Institute in La Jolla and medical retina disease and vitreoretinal surgery specialist at Retina Consultants San Diego] at an ARVO meeting over five years ago. In collaboration with her, we started to establish methods and protocols to achieve light responses in postmortem human retina tissue.”
The researchers used electroretinography to observe the decline in the light-stimulated electrical response of retinal neurons in donor eyes and discovered that hypoxia and acidosis were the two primary inducers of retinal neuron signaling loss. By counteracting these two processes, they were largely able to revive the retinas and restore photoreceptor signaling to other retinal neurons (1). The use of the retina allowed researchers to gain insight into the loss and restoration of not only central vision, but also the wider central nervous system.
The accessible nature of the retina relative to other parts of the central nervous system widens the scope of the results beyond just eyes. “We hope our research will encourage the whole field to start using our approach to study human retinal physiology and how it is affected in aging and disease,” says Vinberg. “I think this could have far-reaching implications not only within vision science, but also in neuroscience in general. Potential applications include screening the effects of drugs on human neuronal tissue, studying how light signals are processed in the human macula, and researching how these processes are impacted by aging or disease.”
In his vision-focused lab, Vinberg and his team still pursue their goal of better understanding the light signaling pathways of the retina with the belief that, though it may be challenging, there is hope for curing retinal degenerative diseases. “We are particularly interested in better understanding the dark adaptation pathways in the human central retina and how they are impacted in AMD. Our approach enables dissecting these mechanisms in the human macula in ways that were not possible before,” he says. “We are also working on understanding the mechanism by which hypoxia causes irreversible loss of coordinated transmission of light signals and what, if anything, we can do to improve the hypoxia resistance of retinal neurons. There is also the far-reaching prospect of photoreceptor or retina transplantation. Currently, there are many barriers to this, one of which is how the grafts can be integrated into the host circuitry. However, the vision science field is currently working on such challenges. Someday, it might be entirely possible to cure blindness via transplantation. What I do know is that, if we don’t try, it will certainly never happen.”
- F Abbas et al., Nature, [Online ahead of print] (2022). PMID: 35545677.