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.
Podcast: The future of brain health with Percy Griffin
Today's guest is Percy Griffin, director of scientific engagement for the Alzheimer’s Association, a nonprofit that’s focused on speeding up research, finding better ways to detect Alzheimer’s earlier and other approaches for reducing risk. Percy has a doctorate in molecular cell biology from Washington University, he’s led important research on Alzheimer’s, and you can find the link to his full bio in the show notes, below.
Our topic for this conversation is the present and future of the fight against dementia. Billions of dollars have been spent by the National Institutes of Health and biotechs to research new treatments for Alzheimer's and other forms of dementia, but so far there's been little to show for it. Last year, Aduhelm became the first drug to be approved by the FDA for Alzheimer’s in 20 years, but it's received a raft of bad publicity, with red flags about its effectiveness, side effects and cost.
Meanwhile, 6.5 million Americans have Alzheimer's, and this number could increase to 13 million in 2050. Listen to this conversation if you’re concerned about your own brain health, that of family members getting older, or if you’re just concerned about the future of this country with experts predicting the number people over 65 will increase dramatically in the very near future.
Listen to the Episode
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4:40 - We talk about the parts of Percy’s life that led to him to concentrate on working in this important area.
6:20 - He defines Alzheimer's and dementia, and discusses the key elements of communicating science.
10:20 - Percy explains why the Alzheimer’s Association has been supportive of Aduhelm, even as others have been critical.
17:58 - We talk about therapeutics under development, which ones to be excited about, and how they could be tailored to a person's own biology.
24:25 - Percy discusses funding and tradeoffs between investing more money into Alzheimer’s research compared to other intractable diseases like cancer, and new opportunities to accelerate progress, such as ARPA-H, President Biden’s proposed agency to speed up health breakthroughs.
27:24 - We talk about the social determinants of brain health. What are the pros/cons of continuing to spend massive sums of money to develop new drugs like Aduhelm versus refocusing on expanding policies to address social determinants - like better education, nutritious food and safe drinking water - that have enabled some groups more than others to enjoy improved cognition late in life.
34:18 - Percy describes his top lifestyle recommendations for protecting your mind.
37:33 - Is napping bad for the brain?
39:39 - Circadian rhythm and Alzheimer's.
42:34 - What tests can people take to check their brain health today, and which biomarkers are we making progress on?
47:25 - Percy highlights important programs run by the Alzheimer’s Association to support advances.
Show links:
** After this episode was recorded, the Centers for Medicare and Medicaid Services affirmed its decision from last June to limit coverage of Aduhelm. More here.
- Percy Griffin's bio: https://www.alz.org/manh/events/alztalks/upcoming-...
- The Alzheimer's Association's Part the Cloud program: https://alz.org/partthecloud/about-us.asp
- The paradox of dementia rates decreasing: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455342/
- The argument for focusing more resources on improving institutions and social processes for brain health: https://www.statnews.com/2021/09/23/the-brain-heal...
- Recent research on napping: https://www.ocregister.com/2022/03/25/alzheimers-s...
- The Alzheimer's Association helpline: https://www.alz.org/help-support/resources/helpline
- ALZConnected, a free online community for people affected by dementia https://www.alzconnected.org/
- TrialMatch for people with dementia and healthy volunteers to find clinical trials for Alzheimer's and other dementia: https://www.alz.org/alzheimers-dementia/research_p...
COVID-19 prompted numerous companies to reconsider their approach to the future of work. Many leaders felt reluctant about maintaining hybrid and remote work options after vaccines became widely available. Yet the emergence of dangerous COVID variants such as Omicron has shown the folly of this mindset.
To mitigate the risks of new variants and other public health threats, as well as to satisfy the desires of a large majority of employees who express a strong desire in multiple surveys for a flexible hybrid or fully remote schedule, leaders are increasingly accepting that hybrid and remote options represent the future of work. No wonder that a February 2022 survey by the Federal Reserve Bank of Richmond showed that more and more firms are offering hybrid and fully-remote work options. The firms expect to have more remote workers next year and more geographically-distributed workers.
Although hybrid and remote work mitigates public health risks, it poses another set of health concerns relevant to employee wellbeing, due to the threat of proximity bias. This term refers to the negative impact on work culture from the prospect of inequality among office-centric, hybrid, and fully remote employees.
The difference in time spent in the office leads to concerns ranging from decreased career mobility for those who spend less facetime with their supervisor to resentment building up against the staff who have the most flexibility in where to work. In fact, a January 2022 survey by the company Slack of over 10,000 knowledge workers and their leaders shows that proximity bias is the top concern – expressed by 41% of executives - about hybrid and remote work.
To address this problem requires using best practices based on cognitive science for creating a culture of “Excellence From Anywhere.” This solution is based on guidance that I developed for leaders at 17 pioneering organizations for a company culture fit for the future of work.
Protect from proximity bias via the "Excellence From Anywhere" strategy
So why haven’t firms addressed the obvious problem of proximity bias? Any reasonable external observer could predict the issues arising from differences of time spent in the office.
Unfortunately, leaders often fail to see the clear threat in front of their nose. You might have heard of black swans: low-probability, high-impact threats. Well, the opposite kind of threats are called gray rhinos: obvious dangers that we fail to see because of our mental blindspots. The scientific name for these blindspots is cognitive biases, which cause leaders to resist best practices in transitioning to a hybrid-first model.
The core idea is to get all of your workforce to pull together to achieve business outcomes: the location doesn’t matter.
Leaders can address this by focusing on a shared culture of “Excellence From Anywhere.” This term refers to a flexible organizational culture that takes into account the nature of an employee's work and promotes evaluating employees based on task completion, allowing remote work whenever possible.
Addressing Resentments Due to Proximity Bias
The “Excellence From Anywhere” strategy addresses concerns about treatment of remote workers by focusing on deliverables, regardless of where you work. Doing so also involves adopting best practices for hybrid and remote collaboration and innovation.
By valuing deliverables, collaboration, and innovation through a focus on a shared work culture of “Excellence From Anywhere,” you can instill in your employees a focus on deliverables. The core idea is to get all of your workforce to pull together to achieve business outcomes: the location doesn’t matter.
This work culture addresses concerns about fairness by reframing the conversation to focus on accomplishing shared goals, rather than the method of doing so. After all, no one wants their colleagues to have to commute out of spite.
This technique appeals to the tribal aspect of our brains. We are evolutionarily adapted to living in small tribal groups of 50-150 people. Spending different amounts of time in the office splits apart the work tribe into different tribes. However, cultivating a shared focus on business outcomes helps mitigate such divisions and create a greater sense of unity, alleviating frustrations and resentments. Doing so helps improve employee emotional wellbeing and facilitates good collaboration.
Solving the facetime concerns of proximity bias
But what about facetime with the boss? To address this problem necessitates shifting from the traditional, high-stakes, large-scale quarterly or even annual performance evaluations to much more frequent weekly or biweekly, low-stakes, brief performance evaluation through one-on-one in-person or videoconference check-ins.
Supervisees agree with their supervisor on three to five weekly or biweekly performance goals. Then, 72 hours before their check-in meeting, they send a brief report, under a page, to their boss of how they did on these goals, what challenges they faced and how they overcame them, a quantitative self-evaluation, and proposed goals for next week. Twenty-four hours before the meeting, the supervisor responds in a paragraph-long response with their initial impressions of the report.
It’s hard to tell how much any employee should worry about not being able to chat by the watercooler with their boss: knowing exactly where they stand is the key concern for employees, and they can take proactive action if they see their standing suffer.
At the one-on-one, the supervisor reinforces positive aspects of performance and coaches the supervisee on how to solve challenges better, agrees or revises the goals for next time, and affirms or revises the performance evaluation. That performance evaluation gets fed into a constant performance and promotion review system, which can replace or complement a more thorough annual evaluation.
This type of brief and frequent performance evaluation meeting ensures that the employee’s work is integrated with efforts by the supervisor’s other employees, thereby ensuring more unity in achieving business outcomes. It also mitigates concerns about facetime, since all get at least some personalized attention from their team leader. But more importantly, it addresses the underlying concerns about career mobility by giving all staff a clear indication of where they stand at all times. After all, it’s hard to tell how much any employee should worry about not being able to chat by the watercooler with their boss: knowing exactly where they stand is the key concern for employees, and they can take proactive action if they see their standing suffer.
Such best practices help integrate employees into a work culture fit for the future of work while fostering good relationships with managers. Research shows supervisor-supervisee relationships are the most critical ones for employee wellbeing, engagement, and retention.
Conclusion
You don’t have to be the CEO to implement these techniques. Lower-level leaders of small rank-and-file teams can implement these shifts within their own teams, adapting their culture and performance evaluations. And if you are a staff member rather than a leader, send this article to your supervisor and other employees at your company: start a conversation about the benefits of addressing proximity bias using such research-based best practices.