Often called the window to the soul, the eyes are more sacred than other body parts, at least for some.
Eye transplants are desperately needed, but they're nowhere in sight. About 12.7 million people worldwide need a corneal transplant, which means that only one in 70 people who require them, get them. The gaps are international. Eye banks in the United Kingdom are around 20 percent below the level needed to supply hospitals, while Indian eye banks, which need at least 250,000 corneas per year, collect only around 45 to 50 thousand donor corneas (and of those 60 to 70 percent are successfully transplanted).
As for retinas, it's impossible currently to put one into the eye of another person. Artificial devices can be implanted to restore the sight of patients suffering from severe retinal diseases, but the number of people around the world with such “bionic eyes” is less than 600, while in America alone 11 million people have some type of retinal disease leading to severe vision loss. Add to this an increasingly aging population, commonly facing various vision impairments, and you have a recipe for heavy burdens on individuals, the economy and society. In the U.S. alone, the total annual economic impact of vision problems was $51.4 billion in 2017.
Even if you try growing tissues in the petri dish route into organoids mimicking the function of the human eye, you will not get the physiological complexity of the structure and metabolism of the real thing, according to Cosma. She is a member of a scientific consortium that includes researchers from major institutions from Spain, the U.K., Portugal, Italy and Israel. The consortium has received about $3.8 million from the European Union to pursue innovative eye research. Her team’s goal is to give hope to at least 2.2 billion people across the world afflicted with a vision impairment and 33 million who go through life with avoidable blindness.
Their method? Resuscitating cadaveric eyes for at least a month.
If we succeed, it will be the first intact human model of the eye capable of exploring and analyzing regenerative processes ex vivo. -- Maria Pia Cosma.
“We proposed to resuscitate eyes, that is to restore the global physiology and function of human explanted tissues,” Cosma said, referring to living tissues extracted from the eye and placed in a medium for culture. Their ECaBox is an ex vivo biological system, in which eyes taken from dead donors are placed in an artificial environment, designed to preserve the eye’s temperature and pH levels, deter blood clots, and remove the metabolic waste and toxins that would otherwise spell their demise.
Scientists work on resuscitating eyes in the lab of Maria Pia Cosma.
Courtesy of Maria Pia Cosma.
“One of the great challenges is the passage of the blood in the capillary branches of the eye, what we call long-term perfusion,” Cosma said. Capillaries are an intricate network of very thin blood vessels that transport blood, nutrients and oxygen to cells in the body’s organs and systems. To maintain the garland-shaped structure of this network, sufficient amounts of oxygen and nutrients must be provided through the eye circulation and microcirculation. “Our ambition is to combine perfusion of the vessels with artificial blood," along with using a synthetic form of vitreous, or the gel-like fluid that lets in light and supports the the eye's round shape, Cosma said.
The scientists use this novel setup with the eye submersed in its medium to keep the organ viable, so they can test retinal function. “If we succeed, we will ensure full functionality of a human organ ex vivo. It will be the first intact human model of the eye capable of exploring and analyzing regenerative processes ex vivo,” Cosma added.
A rapidly developing field of regenerative medicine aims to stimulate the body's natural healing processes and restore or replace damaged tissues and organs. But for people with retinal diseases, regenerative medicine progress has been painfully slow. “Experiments on rodents show progress, but the risks for humans are unacceptable,” Cosma said.
The ECaBox could boost progress with regenerative medicine for people with retinal diseases, which has been painfully slow because human experiments involving their eyes are too risky. “We will test emerging treatments while reducing animal research, and greatly accelerate the discovery and preclinical research phase of new possible treatments for vision loss at significantly reduced costs,” Cosma explained. Much less time and money would be wasted during the drug discovery process. Their work may even make it possible to transplant the entire eyeball for those who need it.
“It is a very exciting project,” said Sanjay Sharma, a professor of ophthalmology and epidemiology at Queen's University, in Kingston, Canada. “The ability to explore and monitor regenerative interventions will increasingly be of importance as we develop therapies that can regenerate ocular tissues, including the retina.”
Seemingly, there's no sacred religious text or a holy book prohibiting the practice of eye donation.
But is the world ready for eye transplants? “People are a bit weird or very emotional about donating their eyes as compared to other organs,” Cosma said. And much can be said about the problem of eye donor shortage. Concerns include disfigurement and healthcare professionals’ fear that the conversation about eye donation will upset the departed person’s relatives because of cultural or religious considerations. As just one example, Sharma noted the paucity of eye donations in his home country, Canada.
Yet, experts like Sharma stress the importance of these donations for both the recipients and their family members. “It allows them some psychological benefit in a very difficult time,” he said. So why are global eye banks suffering? Is it because the eyes are the windows to the soul?
Seemingly, there's no sacred religious text or a holy book prohibiting the practice of eye donation. In fact, most major religions of the world permit and support organ transplantation and donation, and by extension eye donation, because they unequivocally see it as an “act of neighborly love and charity.” In Hinduism, the concept of eye donation aligns with the Hindu principle of daan or selfless giving, where individuals donate their organs or body after death to benefit others and contribute to society. In Islam, eye donation is a form of sadaqah jariyah, a perpetual charity, as it can continue to benefit others even after the donor's death.
Meanwhile, Buddhist masters teach that donating an organ gives another person the chance to live longer and practice dharma, the universal law and order, more meaningfully; they also dismiss misunderstandings of the type “if you donate an eye, you’ll be born without an eye in the next birth.” And Christian teachings emphasize the values of love, compassion, and selflessness, all compatible with organ donation, eye donation notwithstanding; besides, those that will have a house in heaven, will get a whole new body without imperfections and limitations.
The explanation for people’s resistance may lie in what Deepak Sarma, a professor of Indian religions and philosophy at Case Western Reserve University in Cleveland, calls “street interpretation” of religious or spiritual dogmas. Consider the mechanism of karma, which is about the causal relation between previous and current actions. “Maybe some Hindus believe there is karma in the eyes and, if the eye gets transplanted into another person, they will have to have that karmic card from now on,” Sarma said. “Even if there is peculiar karma due to an untimely death–which might be interpreted by some as bad karma–then you have the karma of the recipient, which is tremendously good karma, because they have access to these body parts, a tremendous gift,” Sarma said. The overall accumulation is that of good karma: “It’s a beautiful kind of balance,” Sarma said.
For the Jews, Christians, and Muslims who believe in the physical resurrection of the body that will be made new in an afterlife, the already existing body is sacred since it will be the basis of a new refashioned body in an afterlife.---Omar Sultan Haque.
With that said, Sarma believes it is a fallacy to personify or anthropomorphize the eye, which doesn’t have a soul, and stresses that the karma attaches itself to the soul and not the body parts. But for scholars like Omar Sultan Haque—a psychiatrist and social scientist at Harvard Medical School, investigating questions across global health, anthropology, social psychology, and bioethics—the hierarchy of sacredness of body parts is entrenched in human psychology. You cannot equate the pinky toe with the face, he explained.
“The eyes are the window to the soul,” Haque said. “People have a hierarchy of body parts that are considered more sacred or essential to the self or soul, such as the eyes, face, and brain.” In his view, the techno-utopian transhumanist communities (especially those in Silicon Valley) have reduced the totality of a person to a mere material object, a “wet robot” that knows no sacredness or hierarchy of human body parts. “But for the Jews, Christians, and Muslims who believe in the physical resurrection of the body that will be made new in an afterlife, the [already existing] body is sacred since it will be the basis of a new refashioned body in an afterlife,” Haque said. “You cannot treat the body like any old material artifact, or old chair or ragged cloth, just because materialistic, secular ideologies want so,” he continued.
For Cosma and her peers, however, the very definition of what is alive or not is a bit semantic. “As soon as we die, the electrophysiological activity in the eye stops,” she said. “The goal of the project is to restore this activity as soon as possible before the highly complex tissue of the eye starts degrading.” Cosma’s group doesn’t yet know when they will be able to keep the eyes alive and well in the ECaBox, but the consensus is that the sooner the better. Hopefully, the taboos and fears around the eye donations will dissipate around the same time.
Electricity is emerging as a powerful treatment for chronic ailments.
Kelly, a case manager for an insurance company, spent years battling both migraines and Crohn's, a disease in which the immune system attacks the intestines.
For many people, like Kelly, a stronger electric boost to the vagus nerve could be life-changing.
After she had her large intestine removed, her body couldn't absorb migraine medication. Last year, about twice a month, she endured migraines so bad she couldn't function. "It would go up to a ten, and I would rock, wait it out," she said. The pain might last for three days.
Then her neurologist showed her a new device, gammaCore, that tames migraines by stimulating a nerve—not medication. "I don't have to put a chemical in my body," she said. "I was thrilled."
At first, Kelly used the device at the onset of a migraine, applying electricity to her pulse at the front of her neck for six minutes. The pain peaked at about half the usual intensity--low enough, she said, that she could go to work. Four months ago, she began using the device for two minutes each night as prevention, and she hasn't had a serious migraine since.
The Department of Defense and Veterans Administration now offer gammaCore to patients, but it hasn't yet been approved by Medicare, Medicaid, or most insurers. A month of therapy costs $600 before insurance or a generous financial assistance program kicks in.
A patient uses gammaCore, a non invasive vagal nerve stimulator device that was FDA approved in November 2018, to treat her migraine.
(Photo captured from a patient video at gammacore.com)
If the poet Walt Whitman wrote "I Sing The Body Electric" today, he might get specific and point to the vagus nerve, a bundle of fibers that run from the brainstem down the neck to the heart and gut. Singing stimulates it—and for many people, like Kelly, a stronger electric boost to the nerve could be life-changing.
The mind-body connection isn't just an idea — the vagus nerve literally carries signals from the mind to the body and back. It may explain the link between childhood trauma and illnesses such as chronic pain and headaches in adults. "How is it possible that a psychological event causes pain years later?" asked Peter Staats, co-founder of electroCore, which has won approval for its new device from the Food and Drug Administration (FDA) for both migraine and cluster headaches. "There has to be a mind-body interface, and that is the vagus nerve," he said.
Scientists knew that this nerve controlled your heart rate and blood pressure, but in the past decade it has been linked to both pain and the immune system.
"Everything is gated through the vagus -- problems with the gut, the heart, and the lungs," said Chris Wilson, a researcher at Loma Linda University, in California. Wilson is studying how vagus nerve stimulation (VNS) could help pre-term babies who develop lung infections. "Nearly every one of our chronic diseases, including cancer, Alzheimer's, Parkinson's, chronic arthritis and rheumatoid arthritis, and depression and chronic pain…could benefit from an appropriate stimulator," he said.
It's unfortunate that Kelly got her device only after her large intestine was gone. SetPoint Medical, a privately held California company founded to develop electronic treatments for chronic autoimmune diseases, has announced early positive results with VNS for both Crohn's and rheumatoid arthritis.
As SetPoint's chief medical officer, David Chernoff, put it, "We're hacking into the nervous system to activate a system that is already there," an approach that, he said, could work "on many diseases that are pain- and inflammation-based." Inflammation plays a role in much modern illness, including depression and obesity. The FDA already has approved VNS for both, using surgically implanted devices similar to pacemakers. (GammaCore is external.)
The history of VNS implants goes back to 1997, when the FDA approved one for treating epilepsy and researchers noticed that it rapidly lifted depression in epileptic patients. By 2005, the agency had approved an implant for treatment-resistant depression. (Insurance companies declined to reimburse the approach and it didn't take off, but that might change: in February, the Center for Medicare and Medicaid Services asked for more data to evaluate coverage.) In 2015, the FDA approved an implant in the abdomen to regulate appetite signals and help obese people lose weight.
The link to inflammation had emerged a decade earlier, when researchers at the Feinstein Institute for Medical Research, in Manhasset, New York, demonstrated that stimulating the nerve with electricity in rats suppressed the production of cytokines, a signaling protein important in the immune system. The researchers developed a concept of a hard-wired pathway, through the vagus nerve, between the immune and nervous system. That pathway, they argued, regulates inflammation. While other researchers argue that VNS is helpful by other routes, there is clear evidence that, one way or another, it does affect immunity.
At the same time, investors are seeking alternatives to drugs.
The Feinstein rat research concluded that it took only a minute a day of stimulation and tiny amounts of energy to activate an anti-inflammatory reflex. This means you can use devices "the size of a coffee bean," said Chernoff, much less clunky than current pacemakers—and advances in electronic technology are making them possible.
At the same time, investors are seeking alternatives to drugs. "There's been a push back on drug pricing," noted Lisa Rhoads, a managing director at Easton Capital Investment Group, in New York, which supported electroCore, "and so many unintended consequences."
In 2016, the U.S. National Institutes of Health began pumping money into relevant research, in a program called "Stimulating Peripheral Activity to Relieve Conditions," which focuses on "understanding peripheral nerves — nerves that connect the brain and spinal cord to the rest of the body — and how their electrical signals control internal organ function."
GlaxoSmithKline formed Galvani Bioelectronics with Google to study miniature implants. It had already invested in Action Potential Venture Capital, in Cambridge, Massachusetts, which holds SetPoint and seven other companies "that are all targeting a nerve to treat a chronic disease," noted partner Imran Eba. "I see a future in which bioelectronics medicine is competing directly with drugs," he said.
Treating the body with electricity could bring more ease and lower costs. Many people with serious auto-immune disease, for example, have to inject themselves with drugs that cost $60,000 a year. SetPoint's implant would cost less and only need charging once a week, using a charger worn around the neck, Chernoff said. The company receives notices remotely and can monitor compliance.
Implants also allow the treatment to target a nerve precisely, which could be important with Parkinson's, chronic pain, and depression, observed James Cavuoto, editor and publisher of Neurotech Reports. They may also allow for more fine-turning. "In general, the industry is looking for signals, biomarkers that indicate when is the right time to turn on and turn off the stimulation. It could dramatically increase the effectiveness of the therapy and conserve battery life," he said.
Eventually, external devices could receive data from biomarkers as well. "It could be something you wear on your wrist," Cavuoto noted. Bluetooth-enabled devices could communicate with phones or laptops for data capture. External devices don't require surgery and put the patient in charge. "In the future you'll see more customer specification: Give the patient a tablet or phone app that lets them track and modify their parameters, within a range. With digital devices we have an enormous capability to customize therapies and collect data and get feedback that can be fed back to the clinician," Cavuoto said.
Slow deep breathing, the traditional mind-body intervention, is "like watching Little League. What we're doing is Major League."
It's even possible to stimulate the vagus through the ear, where one branch of the bundle of fibers begins. In a fetus, the tissue that becomes the ear is also part of the vagus nerve, and that one bit remains. "It's the same point as the acupuncture point," explained Mark George, a psychiatrist and pioneer researcher in depression at Medical University of South Carolina in Charleston. "Acupuncture figured out years ago by trial and error what we're just learning about now."
Slow deep breathing, the traditional mind-body intervention, also affects the vagus nerve in positive ways, but gently. "That's like watching Little League," Staats, the co-founder of electroCore, said. "What we're doing is Major League."
In ten years, researcher Wilson suggested, you could be wearing "a little ear cuff" that monitors your basic autonomic tone, a heart-attack risk measure governed in part by the vagus nerve. If your tone looked iffy, the stimulator would intervene, he said, "and improve your mood, cognition, and health."
In the meantime, we can take some long slow breaths, read Whitman, and sing.
