Vision loss from retinal disease is one of the biggest challenges in eye health today. At the root of the problem is a loss of balance in the immune cells of the retina. When inflammation takes over, tiny immune cells called microglia that are normally protective switch into overdrive and start causing harm instead of helping.
This chain reaction creates an unhealthy environment that leads to abnormal blood vessel growth and scarring—damage that can cause permanent vision loss.
Anton Lennikov, MD, PhD, a physician-investigator at the Schepens Eye Research Institute at Mass Eye and Ear, is leading innovative research strategies designed to slow the disease and help the retina heal itself.
His lab uses innovative approaches such as advanced human tissue models, precision immunotherapies, and even gentle electrical stimulation—all with one goal: Restoring sight.
In this Q&A, we take a closer look at the science behind these new approaches, the challenges of studying inflammation in the eye and what these findings could mean for the future of vision care.
(The image above, taken by Anton Lennikov, PhD, shows ex-vivo RPE/Chroidal explants. The human neovascular AMD condition remains preserved in ex-vivo RPE/Choroidal explants. This preservation is critical because it allows researchers to study disease mechanisms and test potential therapies in a system that closely mimics the human pathological environment.)
Q: What inspired you to focus on diseases of the eye and retinal degeneration?
Anton Lenninkov, MD, PhD
A: The eye is one of the few tissues where you can watch disease unfold in real time.
Retinal pathology sits at the intersection of neurobiology, vascular biology and immunology—three systems that rarely reveal themselves so clearly anywhere else in the body.
Early in my career, I realized that even subtle changes in microglia or endothelial function (the ability of blood vessel linings to regulate flow and barrier integrity) can trigger a chain of events leading to vision loss, and that this presented an opportunity.
If we can understand those mechanisms precisely, we can intervene before irreversible damage occurs. Decoding this complex challenge to protect sight is what drives my work in this field.
Q: Can you explain why angiogenesis and microglial activation are so critical in eye health?
A: The eye is one of the most metabolically active tissues in the body. Constant exposure to light and high oxidative stress means that it needs ongoing repair to stay healthy.
Photoreceptor outer segments—the light-sensitive parts of retinal cells—wear out quickly (at a rate of 8-10% per day), requiring constant renewal.
The retina also demands an exceptionally high supply of oxygen and nutrients, making its blood vessels among the most specialized in the body.
In this demanding environment, microglia are responsible for clearing waste, repairing oxidative damage, supporting neurons and maintaining balance across these complex systems.
When functioning properly, microglia protect retinal neurons and blood vessels.
But aging, stress or disease can push microglia into overdrive, causing harm instead. They release inflammatory signals and promote abnormal blood vessel growth and scarring.
Blood vessels, trying to compensate for this additional stress, can also disrupt the retina’s structure.
Over time, uncontrolled microglial activity and abnormal vascular responses break down retinal balance, leading to degeneration, harmful vessel growth and vision loss.
Controlling these processes offers a path to preserving vision and preventing diseases such as neovascular age-related macular degeneration (AMD) and diabetic retinopathy.
My work focuses on stopping this harmful interaction.
Q: What are the biggest challenges in studying neuroinflammation within the retina?
A: The biggest challenges in studying neuroinflammation in the eye are getting access to the tissue, achieving high enough resolution to see fine details and ensuring that findings are truly relevant to human disease.
Microglial activation happens deep inside the retina’s layered neural tissue, which is hard to access without disrupting the system. This means researchers often rely on lab models or post-mortem human tissues.
However, most models don’t quite mimic the slow, low-level inflammation seen in human aging and AMD.
These challenges led me to develop advanced human RPE/choroid explant systems that can bring small sections of donated human eyes back to life to be able to study them.
Remarkably, these living tissue samples keep the disease features of the donor’s eye, including conditions like neovascular AMD and diabetic retinopathy, and respond to known treatments.
Working with an outstanding research team at the Schepens Eye Research Institute —Leo Kim, MD, PhD, Dong Feng Chen, MD, PhD, and William Miller, PhD—we turned this ambitious idea into a practical research platform.
I believe it will become widely used by scientists and the pharmaceutical industry.
Q: What potential do your findings hold for treating AMD or diabetic retinopathy?
A: My research suggests the most effective strategy is to stop abnormal blood vessel growth (angiogenesis) at its source by controlling inflammation in the retina.
Doing this can also reduce scarring (fibrosis), which is currently very hard to treat and is a major cause of permanent vision loss. These new therapies could work alongside anti-VEGF drugs (medications that block a protein that promotes the growth of leaky, abnormal blood vessels), or serve as alternatives when those drugs don’t work.
By shifting immune and metabolic states in the eye, we may achieve longer-lasting results than repeated VEGF treatments alone.
In short, the real potential lies in targeting the root causes of disease—not just the symptoms that appear later.
Q: What has been the most surprising finding in your research so far?
A: One of the most surprising discoveries has been how strongly electrical stimulation can change cell behavior.
We usually think of electricity as a rough tool that doesn’t work well with biology, but in the retina it acts with surprising precision. It can calm overactive microglia, change how cells use energy, and stop abnormal blood vessel growth.
Seeing microglia and blood vessel cells completely change their signals, energy production, and inflammation just because of an electric field showed me how adaptable these immune cells are—and how much electric currents can influence the body.
Another surprise has been working with donated human eye tissue. We often think death happens instantly, but biologically it’s a slow process that takes days.
When we revive small pieces of human eye tissue, they remain remarkably alive, keep the disease traits of the donor, and respond to treatments.
For example, tissue from a donor with neovascular age-related macular degeneration (AMD) still shows abnormal vessel growth and scarring days after death, while healthy tissue behaves normally.
Realizing that human tissue preserves its disease identity long after death has opened the door to experimental systems we never imagined possible. This discovery is both scientifically fascinating and deeply thought-provoking.
In this video, you’ll see a piece of human eye tissue—specifically the RPE and choroid—growing fibrotic tissue and tiny blood vessels in culture. The time-lapse runs for 36 hours, with each frame captured every 5 minutes.
We took a small sample from the back of the eye and placed it in a controlled environment. Over time, it started forming scar-like tissue and new blood vessels, which are key features in diseases like macular degeneration.
Fun questions that may (or may not) be about science!
Q: If you could teleport anywhere right now, where would you go?
A: If we take “teleport anywhere” literally, I would choose a spot one astronomical unit away from Sagittarius A, the supermassive black hole at the center of our galaxy. From that safe distance—far enough to avoid its intense gravitational pull—it would be possible to observe this incredible object directly. For any scientist, that would be one of the most extraordinary sights imaginable
On a more practical, Earth-based level, I would choose a place where science and nature meet in a way that inspires clear thinking—somewhere like the European Alps, coastal Japan, or the glaciers of northern Iceland. These environments naturally encourage reflection and long-term perspective.
As scientists, we spend most of our time in controlled lab spaces, but many of the most important ideas come when we step away from routine and give our minds room to reset.
Q: What’s the most memorable trip you’ve ever taken?
A: Moving to Japan for my PhD, which wasn’t a typical trip—it was a full transition to a new country, language, and culture.
Living in Sapporo and working in a Japanese lab fundamentally changed how I think about science. The precision, discipline, and attention to detail I saw there set a new standard for my own work. Outside the lab, everyday life was just as transformative: Learning the language, handling Hokkaido’s winters and even getting a driver’s license.
That period taught me resilience and independence, and how to build a life from the ground up in an unfamiliar place. Many of the research directions I later pursued—especially in retinal biology and inflammation—trace back to ideas and experiences from that time.
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Amazing and inspiring work Dr. Lenninkov!