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.
Epigenetic therapeutics could revolutionize medicine in the coming decades. (© kentoh/Adobe)
How exactly does your DNA make you who you are?
It's because of epigenetics that identical twins can actually look different and develop different diseases.
Just as software developers don't write apps out of ones and zeros, the interesting parts of the human genome aren't written merely in As, Ts, Cs and Gs. Yes, these are the fundamental letters that make up our DNA and encode the proteins that make our cells function, but the story doesn't end there.
Our cells possess amazing abilities, like eating invading bacteria or patching over a wound, and these abilities require the coordinated action of hundreds, if not thousands, of proteins. Epigenetics, the study of gene expression, examines how multiple genes work at once to make these biological processes happen.
It's because of epigenetics that identical twins – who possess identical DNA -- can actually look different and develop different diseases. Their environments may influence the expression of their genes in unique ways. For example, a research study in mice found that maternal exposure to a chemical called bisphenol A (BPA) resulted in drastic differences between genetically identical offspring. BPA exposure increased the likelihood that a certain gene was turned on, which led to the birth of yellow mice who were prone to obesity. Their genetically identical siblings who were not exposed to BPA were thinner and born with brown fur.
These three mice are genetically identical. Epigenetic differences, however, result in vastly different phenotypes.
(© 1994 Nature Publishing Group, Duhl, D.)
This famous mouse experiment is just one example of how epigenetics may transform medicine in the coming years. By studying the way genes are turned on and off, and maybe even making those changes ourselves, scientists are beginning to approach diseases like cancer in a completely new way.
With few exceptions, most of the 1 trillion cells that make up your body contain the same DNA instructions as all the others. How does each cell in your body know what it is and what it has to do? One of the answers appears to lie in epigenetic regulation. Just as everyone at a company may have access to all the same files on the office Dropbox, the accountants will put different files on their desktop than the lawyers do.
Our cells prioritize DNA sequences in the same way, even storing entire chromosomes that aren't needed along the wall of the nucleus, while keeping important pieces of DNA in the center, where it is most accessible to be read and used. One of the ways our cells prioritize certain DNA sequences is through methylation, a process that inactivates large regions of genes without editing the underlying "file" itself.
As we learn more about epigenetics, we gain more opportunities to develop therapeutics for a broad range of human conditions, from cancer to metabolic disorders. Though there have not been any clinical applications of epigenetics to immune or metabolic diseases yet, cancer is one of the leading areas, with promising initial successes.
One of the challenges of cancer treatments is that different patients may respond positively or negatively to the same treatment. With knowledge of epigenetics, however, doctors could conduct diagnostic tests to identify a patient's specific epigenetic profile and determine the best treatment for him or her. Already, commercial kits are available that help doctors screen glioma patients for an epigenetic biomarker called MGMT, because patients with this biomarker have shown high rates of success with certain kinds of treatments.
Other epigenetic advances go beyond personalized screening to treatments targeting the mechanism of disease. Some epigenetic drugs turn on genes that help suppress tumors, while others turn on genes that reveal the identity of tumor cells to the immune system, allowing it to attack cancerous cells.
Direct, targeted control of your epigenome could allow doctors to reprogram cancerous or aging cells.
The study of epigenetics has also been fundamental to the field of aging research. The older you get, the more methylation marks your DNA carries, and this has led to the distinction between biological aging, or the state of your cells, and chronological aging, or how old you actually are.
Just as our DNA can get miscopied and accumulate mutations, errors in DNA methylation can lead to so-called "epimutations". One of the big hypotheses in aging research today is that the accumulation of these random epimutations over time is responsible for what we perceive as aging.
Studies thus far have been correlative - looking at several hundred sites of epigenetic modifications in a person's cell, scientists can now roughly discern the age of that person. The next set of advances in the field will come from learning what these epigenetic changes individually do by themselves, and if certain methylations are correlated with cellular aging. General diagnostic terms like "aging" could be replaced with "abnormal methylation at these specific locations," which would also open the door to new therapeutic targets.
Direct, targeted control of your epigenome could allow doctors to reprogram cancerous or aging cells. While this type of genetic surgery is not feasible just yet, current research is bringing that possibility closer. The Cas9 protein of genome-editing CRISPR/Cas9 fame has been fused with epigenome modifying enzymes to target epigenetic modifications to specific DNA sequences.
A therapeutic of this type could theoretically undo a harmful DNA methylation, but would also be competing with the cell's native machinery responsible for controlling this process. One potential approach around this problem involves making beneficial synthetic changes to the epigenome that our cells do not have the capacity to undo.
Also fueling this frontier is a new approach to understanding disease itself. Scientists and doctors are now moving beyond the "one defective gene = one disease" paradigm. Because lots of diseases are caused by multiple genes going haywire, epigenetic therapies could hold the key to new types of treatments by targeting multiple defective genes at once.
Scientists are still discovering which epigenetic modifications are responsible for particular diseases, and engineers are building new tools for epigenome editing. Given the proliferation of work in these fields within the last 10 years, we may see epigenetic therapeutics emerging within the next couple of decades.
