A major federal grant is funding a promising new approach to treating dry age-related macular degeneration, a leading cause of blindness in older adults, using engineered stem cells that can evade the immune system without requiring patients to take immune-suppressing drugs for life. The National Eye Institute awarded Oregon Health & Science University researcher Trevor McGill a five-year, nearly $4.2 million grant to advance stem cell-based treatments for the disease, which affects roughly one-third of adults older than 75.

What Makes This Approach Different From Current Treatments?

Dry age-related macular degeneration, or AMD, accounts for 90% of advanced cases of the disease, yet effective therapies remain limited. The condition involves the gradual death of retinal pigment epithelial cells, or RPE cells, which support the light-sensing cells of the retina. Once these cells are lost, they do not naturally regenerate, leading to progressive vision loss and blindness. Current treatments are limited to dietary and lifestyle changes, with no effective drug therapies available.

For decades, scientists have explored replacing damaged retinal cells with healthy stem cell-derived cells, but a major obstacle has stood in the way: the immune system rejects transplanted cells, even when donor and recipient are the same species. Most experimental cell therapies rely on immune-suppressing medications to prevent rejection, which poses serious challenges for older patients who may already have other health conditions.

"Many patients with AMD are in their late 70s or 80s. The last thing you want is to force someone to choose between protecting their eyesight and dealing with the risks associated with long-term immune suppression," said Trevor McGill, associate professor in the Division of Neuroscience at the Oregon National Primate Research Center and research associate professor in the OHSU Casey Eye Institute.

Trevor McGill, Associate Professor, Oregon Health & Science University

McGill's laboratory is developing what researchers call "hypoimmune" or "universal donor" stem cells. These cells are engineered to hide from the immune system, allowing them to survive after transplantation without provoking a strong immune response. The grant will support studies evaluating the long-term survival, safety, and effectiveness of these cells in nonhuman primate models of retinal disease.

How Does This Engineered Cell Technology Work?

• Immune Evasion: Researchers engineer the stem cells to avoid detection by the immune system, allowing transplanted cells to survive without triggering rejection responses that would otherwise destroy them within days or weeks.
• Built-in Safety Switches: The engineered cells include safety mechanisms designed to eliminate transplanted cells if unexpected problems occur, providing an additional layer of protection as these technologies move toward clinical applications.
• Primate Model Testing: Unlike rodent models, nonhuman primates develop age-related macular degeneration naturally and have eye biology that more closely resembles humans, making them ideal for testing whether these therapies will work in people.

"This is really about solving one of the biggest barriers facing regenerative medicine. We know stem cell-derived therapies have enormous potential, but if the immune system rejects those transplanted cells, the benefits are short-lived. Our lab is developing cells that can essentially avoid immune detection while maintaining important safety controls," McGill explained.

Trevor McGill, Associate Professor, Oregon Health & Science University

McGill's team has already demonstrated in previous research that transplanted retinal cells can be rapidly rejected by the immune system. The new project builds on years of work developing these hypoimmune cells and will test whether the safety switches can selectively remove transplanted cells if necessary.

Why Is This Research Personal for the Lead Scientist?

The work reflects deep personal motivation for McGill. His grandmother lost much of her vision due to AMD, and he watched the disease affect her independence and quality of life. Like many scientists, McGill has a personal connection to the condition he studies, an experience that has stayed with him throughout his career.

The award represents the latest milestone in a translational vision research program built between the Oregon National Primate Research Center and the OHSU Casey Eye Institute. The partnership brings together expertise in retinal gene therapy, stem cell biology, transplantation immunology, and advanced retinal imaging. The goal is to move promising therapies through preclinical testing toward human clinical trials.

What Could This Mean Beyond Eye Disease?

McGill believes the technologies developed through the grant could have broader applications across regenerative medicine. If researchers can create stem cell-derived therapies that safely evade immune rejection, that platform could eventually extend far beyond ophthalmology to treat many diseases that currently have limited treatment options.

For the millions of older adults facing vision loss from AMD, this research offers hope that one day they may be able to preserve their sight without the burden of lifelong immune-suppressing medications. While the work is still in preclinical stages, the substantial federal investment signals confidence that these approaches could eventually reach patients who desperately need new treatment options.