Spark of afterlife points to new hope for blindness

Researchers have discovered a way to revive the eyes of organ donors after death, a breakthrough that paves the way for progress against age-related macular degeneration, glaucoma and other major causes of blindness.

The accomplishment, which many experts had not believed possible, gives scientists the ability for the first time to conduct experiments on a functional human retina, potentially unlocking a treasure trove of new information about the chemistry of vision and what does not go into the complex network. retinal cells when people begin to lose their sight.

“If you don’t understand what the fundamental basis of these abnormalities is, you won’t be able to identify drugs or other treatments that might treat these conditions,” said Anne Hanneken, associate professor of molecular medicine at the Scripps Research Institute, La Jolla, California, and co-leader of the effort.

The achievement may also help advance the prospects for eye transplants, although Dr Hanneken warned that such potential treatments are many years away. For decades, doctors have been able to transplant corneas from donor eyes, but this outer layer of the eye that helps focus has no blood supply and isn’t directly connected to neurons. retinals that send visual signals to the brain. Getting eyes or transplanted retinal tissue to communicate with the brain is a daunting challenge.

Ambitious research is underway in the field of ophthalmology to find new ways to prevent, slow or treat vision loss. Strategies range from developing drugs that protect people with vision loss from further damage, to restoring vision through cell and gene therapies that would replace, regenerate or repair retinal neurons that no longer function. The first approval of any gene therapy came in 2018 for a mutation that causes blindness.

Anne Hanneken, associate professor of molecular medicine at the Scripps Research Institute, is co-lead of the effort to bring organ donors back to life.


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Stephanie Sundell

More than 7 million Americans of all ages live with visual loss, according to a study published last year in JAMA ophthalmology, of which more than a million are blind. The toll is rising, partly reflecting an aging population and a high prevalence of diabetes, a precursor to diseases such as glaucoma and diabetic retinopathy. Worldwide, more than 250 million people have vision loss while another 43 million are blind.

Sight begins when light passes through the cornea and lens and reaches neurons called photoreceptors that live in the retina at the back of the eye. It takes a continuous network of other retinal cells – each with distinct roles – to process light signals and transmit them via the optic nerve to the brain, which converts the data into the clear, focused and colorful images we see.

Eye diseases such as glaucoma, age-related macular degeneration, and hereditary retinitis pigmentosa impair vision by damaging or killing various retinal cells. A class of drugs including Eylea and Roche Holding of Regeneron Inc. AG

Lucentis can be injected into the eye to treat wet age-related macular degeneration, the most advanced and debilitating form of AMD and the leading cause of irreversible reading loss and blindness in older people. The disease damages a layer of neurons called the retinal pigment epithelium, which is crucial for the survival of photoreceptors. The injections stunt the growth of abnormal, leaky blood vessels that develop under the macula region of the retina, responsible for clear central vision.

But the drugs don’t affect dry AMD, the most common and earliest stage of AMD, and may be less effective against a host of genetic alterations that each represent a different variant of the disease.

“We hit everything with the same hammer,” said Julia Haller, chief ophthalmologist at Wills Eye Hospital in Philadelphia. “A more sophisticated understanding that potentially leads to more drug targets and more personal approaches would be fantastic.”

The same would be true, for example, to better understand the early stages of macular degeneration, where treatments are needed to protect against the disease getting worse. “You can imagine doing experiments on organ donor tissue from people with early macular degeneration,” said Joan Miller, chief of ophthalmology at Harvard-affiliated Massachusetts Eye and Ear. “That might help you figure out what some of the early stages are” in the condition.

For decades, researchers have relied heavily on mouse studies to help understand the basis of human eye disease. But mice can’t see in color. “They don’t even have a macula, and they don’t have macular degeneration,” said Dr. Hanneken, who is also a retinal surgeon at Scripps Memorial Hospital, La Jolla. “You want a model that mimics human disease.”

This was the motivation behind Dr. Hanneken’s six-year quest to bring Dead Eyes back to life. It attracted skeptics. Trying to revive dead nerve cells has challenged the fundamental belief that neuron death is irreversible.

But his research with eyes obtained after autopsy convinced Dr. Hanneken that some metabolic activity persisted at least briefly after death. Experiments with mice and human post-mortem eyes showed that oxygen loss and acidity changes were the main culprits for the rapid death of retinal cells.

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She began a collaboration with Frans Vinberg, a neuroscientist at the University of Utah, who built a container similar to the coolers used by transplant surgeons to transport organs retrieved from donors. The container is fitted with tiny reservoirs (which researchers typically fill at a scuba diving shop) to deliver oxygen to donor eyes. The eyes are also bathed in a cocktail of nutrients meant to normalize acidity and wake up retinal cells and restore their function.

For about two years, the researchers obtained donated eyes from multiple sources and transported them in the container to their lab for testing. Other than an occasional small electrical signal, they received nothing. The problem, they concluded: Too much time had elapsed between the donor’s death and the eye collection.

Then an organ donor organization agreed to allow Dr. Hanneken to retrieve the eyes of patients who were declared brain dead but remained on life support to keep their hearts and other organs viable for transplant.

“It changed everything,” she said. In eyes recovered within 30-60 minutes after life support was removed, the researchers were able to detect the entire cascade of light signaling through the macula region of the retina – photoreceptors that first absorb light neurons that send signals to the brain. While doctors can measure these signals to diagnose vision loss in patients, the new research now enables experiments and drug testing on donor eyes that would not be possible on living people. Details of the effort were published in the journal Nature in May.

The researchers couldn’t prove that the revived eyes could actually see. “Eyes can react to light, [but] they can’t read the Wall Street Journal headlines,” Dr. Hanneken said. “They are not connected to a brain.” So far, the revived eyes have remained viable for research for up to 24 hours, she said.

Efforts to analyze the data stream from the light signals have already shown promise for learning more about the molecular abnormalities associated with various retinal diseases and for designing ways to treat them, she said.

Indeed, having access to resuscitated human retinal tissue marks a breakthrough that “will help us better understand how these cells function and influence this response with drugs or changes in gene expression to allow them to function better.” , said Akrit Sodhi, an ophthalmologist and researcher. at Johns Hopkins Medicine, Baltimore, which was not involved in the research.

Dr Hanneken thinks the research has implications beyond ophthalmology: If retinal neurons can be brought back to life, what about central nervous system cells associated with other diseases? She has already started discussions with scientists looking for ways to overcome neuron damage associated with strokes and Parkinson’s and Alzheimer’s diseases.

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