Scientists are working on eye transplants for vision loss. Who will sign up?
Awash in a fluid finely calibrated to keep it alive, a human eye rests inside a transparent cubic device. This ECaBox, or Eyes in a Care Box, is a one-of-a-kind system built by scientists at Barcelona’s Centre for Genomic Regulation (CRG). Their goal is to preserve human eyes for transplantation and related research.
In recent years, scientists have learned to transplant delicate organs such as the liver, lungs or pancreas, but eyes are another story. Even when preserved at the average transplant temperature of 4 Centigrade, they last for 48 hours max. That's one explanation for why transplanting the whole eye isn’t possible—only the cornea, the dome-shaped, outer layer of the eye, can withstand the procedure. The retina, the layer at the back of the eyeball that turns light into electrical signals, which the brain converts into images, is extremely difficult to transplant because it's packed with nerve tissue and blood vessels.
These challenges also make it tough to research transplantation. “This greatly limits their use for experiments, particularly when it comes to the effectiveness of new drugs and treatments,” said Maria Pia Cosma, a biologist at Barcelona’s Centre for Genomic Regulation (CRG), whose team is working on the ECaBox.
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.
Your surgery could harm yourself and the planet. Here's what some doctors are doing about it.
This is part 1 of a three part series on a new generation of doctors leading the charge to make the health care industry more sustainable - for the benefit of their patients and the planet. Read part 2 here and part 3 here.
Susanne Koch, an anesthesiologist and neurologist, reached a pivot point when she was up to her neck in water, almost literally. The basement of her house in Berlin had flooded in the summer of 2018, when Berlin was pummeled by unusually strong rains. After she drained the house, “I wanted to dig into facts, to understand how exactly these extreme weather events are related to climate change,” she says.
Studying the scientific literature, she realized how urgent the climate crisis is, but the biggest shock was to learn that her profession contributed substantially to the problem: Inhalation gases used during medical procedures are among the most damaging greenhouse gases. Some inhalation gases are 3,000 times more damaging for the climate than CO2, Koch discovered. “Spending seven hours in the surgery room is the equivalent of driving a car for four days nonstop,” she says. Her job of helping people at Europe’s largest university hospital, the Charité in Berlin, was inadvertently damaging both the people and the planet.
“Nobody had ever even mentioned a word about that during my training,” Koch says.
On the whole, the medical sector is responsible for a disproportionally large percentage of greenhouse gas emissions, with the U.S. as the biggest culprit. According to a key paper published in 2020 in Health Affairs, the health industry “is among the most carbon-intensive service sectors in the industrialized world,” accounting for between 4.4 percent and 4.6 percent of greenhouse gas emissions. “It’s not just anesthesia but health care that has a problem,” says Jodi Sherman, anesthesiology professor and Medical Director of the Program on Healthcare Environmental Sustainability at Yale University as well as co-director of the Lancet Planetary Health Commission on Sustainable Healthcare. In the U.S., health care greenhouse gas emissions make up about 8.5 percent of domestic greenhouse gas emissions. They rose 6 percent from 2010 to 2018, to nearly 1,700 kilograms per person, more than in any other nation.
Of course, patients worry primarily about safety, not sustainability. Yet, Koch emphasizes that “as doctors, we have the responsibility to do no harm, and this includes making sure that we use resources as sustainably as possible.” Studies show that 2018 greenhouse gas and toxic air pollutant emissions resulted in the loss of 388,000 disability-adjusted life years in the U.S. alone. “Disease burden from health care pollution is of the same order of magnitude as deaths from preventable medical errors, and should be taken just as seriously,” Sherman cautions.
When Koch, the anesthesiologist, started discussing sustainable options with colleagues, the topic was immediately met with plenty of interest. Her experience is consistent with the latest representative poll of the nonprofit Foundation Health in Germany. Nine out of ten doctors were interested in urgently finding sustainable solutions for medical services but lacked knowhow and resources. For teaching purposes, Sherman and her team have developed the Yale Gassing Greener app that allows anesthesiologists to compare how much pollution they can avoid through choosing different anesthesia methods. Sherman also published professional guidelines intended to help her colleagues better understand how various methods affect carbon emissions.
Significant traces of inhalation gases have been found in Antarctica and the Himalayas, far from the vast majority of surgery rooms.
A solution espoused by both Sherman and Koch is comparatively simple: They stopped using desflurane, which is by far the most damaging of all inhalation gases to the climate. Its greenhouse effect is 2,590 times stronger than carbon dioxide. The Yale New Haven Hospital already stopped using desflurane in 2013, becoming the first known healthcare organization to eliminate a drug based on environmental grounds. Sherman points out that this resulted in saving more than $1.2 million in costs and 1,600 tons of CO2 equivalents, about the same as the exhaust from 360 passenger vehicles per year.
At the Charité, Koch claims that switching to other anesthesiology choices, such as propofol, has eliminated 90 percent of the climate gas emissions in the anesthesiology department since 2016. Young anesthesiologists are still taught to use desflurane as the standard because desflurane is absorbed less into the patients’ bodies, and they wake up faster. However, Koch who has worked as an anesthesiologist since 2006, says that with a little bit of experience, you can learn when to stop giving the propofol so it's timed just as well with a person’s wake-up process. In addition, “patients are less likely to feel nauseous after being given propofol,” Koch says. Intravenous drugs might require more skill, she adds, "but there is nothing unique to the drug desflurane that cannot be accomplished with other medications.”
Desflurane isn’t the only gas to be concerned about. Nitrous oxide is the second most damaging because it’s extremely long-lived in the environment, and it depletes the ozone layer. Climate-conscious anesthesiologists are phasing out this gas, too, or have implemented measures to decrease leaks.
Internationally, 192 governments agreed in the Kyoto protocol of 2005 to reduce halogenated hydrocarbons – resulting from inhalation gases, including desflurane and nitrous oxide – because of their immense climate-warming potential, and in 2016, they pledged to eliminate them by 2035. However, the use of inhalation anesthetics continues to increase worldwide, not least because more people access healthcare in developing countries, and because people in industrialized countries live longer and therefore need more surgeries. Significant traces of inhalation gases have been found in Antarctica and the Himalayas, far from the vast majority of surgery rooms.
Certain companies are now pushing new technology to capture inhalation gases before they are released into the atmosphere, but both Sherman and Koch believe marketing claims of 99 percent efficiency amount to greenwashing. After investigating the technology first-hand and visiting the company that is producing such filters in Germany, Koch concluded that such technology only reduces emissions by 25 percent. And Sherman believes such initiatives are akin to the fallacy of recycling plastic. In addition to questioning their efficiency, Sherman fears such technology “gives the illusion there is a magical solution that means I don’t need to change my behavior, reduce my waste and choose less harmful options.”
Financial interests are at play, too. “Desflurane is the most expensive inhalation gas, and some think, the most expensive must be the best,” Koch says. Both Koch and Sherman lament that efforts to increase sustainability in the medical sector are entirely voluntary in their countries and led by a few dedicated individual professionals while industry-wide standards and transparency are needed, a notion expressed in the American Hospital Association’s Sustainability Roadmap.
Susanne Koch, an anesthesiologist in Berlin, wants her colleagues to stop using a gas called desflurane, which is by far the most damaging of all inhalation gases to the climate.
Adobe Stock
Other countries have done more. The European Union recommends reducing inhalation gases and even contemplated a ban of desflurane, except in medical emergencies. In 2008, the National Health Service (NHS) created a Sustainable Development Unit, which measures CO2 emissions in the U.K. health sector. NHS is the first national health service that pledged to reach net zero carbon by 2040. The carbon footprint of the NHS fell by 26 percent from 1990 to 2019, mostly due to reduced use of certain inhalers and the switch to renewable energy for heat and power. “The evidence that the climate emergency is a health emergency is overwhelming,” said Nick Watts, the NHS Chief Sustainability Officer, in a press release, “with health professionals already needing to manage its symptoms.”
Sherman is a leading voice in demanding action in the U.S. To her, comprehensive solutions start with the mandatory, transparent measurement of emissions in the health sector to tackle the biggest sources of pollution. While the Biden administration highlighted its efforts to reduce these kinds of emissions during the United Nations Climate Conference (COP27) in November 2022 and U.S. delegates announced that more than 100 health care organizations signed the voluntary Health Sector Climate Pledge, with the aim to reduce emissions by 50 percent in the next eight years, Sherman is convinced that voluntary pledges are not enough. “Voluntary measures are insufficient,” she testified in congress. “The vast majority of U.S. health care organizations remain uncommitted to timely action. Those that are committed lack policies and knowledge to support necessary changes; even worse, existing policies drive inappropriate consumption of resources and pollution.”
Both Sherman and Koch look at the larger picture. “Health care organizations have an obligation to their communities to protect public health,” Sherman says. “We must lead by example. That includes setting ambitious, science-based carbon reduction targets to achieve net zero emissions before 2050. We must quantify current emissions and their sources, particularly throughout the health care supply chains.”
Have You Heard of the Best Sport for Brain Health?
The Friday Five covers five stories in research that you may have missed this week. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on scientific creativity and progress to give you a therapeutic dose of inspiration headed into the weekend.
Listen on Apple | Listen on Spotify | Listen on Stitcher | Listen on Amazon | Listen on Google
Here are the promising studies covered in this week's Friday Five:
- Reprogram cells to a younger state
- Pick up this sport for brain health
- Do all mental illnesses have the same underlying cause?
- New test could diagnose autism in newborns
- Scientists 3D print an ear and attach it to woman