National Institutes of Health scientists have developed a groundbreaking surgical technique that allows for the implantation of multiple tissue grafts in the eye's retina, potentially revolutionizing treatment approaches for dry age-related macular degeneration (AMD). The research, published in JCI Insight, addresses a critical limitation in current cell therapy approaches and may enable higher doses and combinations of therapeutic interventions for this leading cause of vision loss among older Americans.
Addressing Current Surgical Limitations
Until now, surgeons have been restricted to placing only one graft in the retina, significantly limiting both the treatable area in patients and the ability to conduct crucial side-by-side comparisons in animal models. These comparative studies are essential for confirming that tissue grafts properly integrate with the retina and its underlying blood supply network, known as the choriocapillaris.
The research team, led by Dr. Kapil Bharti, scientific director of the National Eye Institute (NEI), designed an innovative surgical clamp that maintains optimal eye pressure during the insertion of two tissue patches in immediate succession while minimizing damage to surrounding tissue.
Breakthrough in Retinal Regeneration
In their animal studies, the scientists utilized the newly developed surgical technique to compare two different grafts placed sequentially within the same experimentally induced AMD-like lesion. The first graft consisted of retinal pigment epithelial (RPE) cells grown on a biodegradable scaffold. RPE cells play a crucial role in supporting and nourishing the retina's light-sensing photoreceptors, and their loss alongside photoreceptors is characteristic of AMD-related vision deterioration.
The RPE cells used in the study were derived from human blood cells that had been converted into stem cells in laboratory conditions. The second graft served as a control, consisting solely of the biodegradable scaffold without cells.
Significant Therapeutic Outcomes
Post-surgical analysis using artificial intelligence to examine retinal images revealed compelling results. The RPE grafts demonstrated significant efficacy in promoting photoreceptor survival, while photoreceptors near scaffold-only grafts experienced substantially higher death rates.
Perhaps most significantly, researchers confirmed for the first time that RPE grafts successfully regenerated the choriocapillaris, the critical network of tiny blood vessels that supplies the retina with essential oxygen and nutrients. This regeneration represents a major advancement in understanding the therapeutic potential of RPE cell therapy.
Clinical Translation and Future Implications
The findings directly support and expand upon capabilities demonstrated in an ongoing NIH-led first-in-human clinical trial of patient-derived RPE grafts for dry AMD. The ability to implant multiple grafts could potentially allow for treatment of larger retinal areas and enable combination therapies that target different aspects of AMD pathology.
Dr. Bharti noted that this technique may enable higher doses and combinations of cell therapies, potentially improving outcomes for patients with advanced dry AMD. The research represents a significant step forward in translating laboratory discoveries into clinical applications for vision restoration.
Research Support and Institutional Context
The work was supported by the National Eye Institute Intramural Research Program. NEI leads federal efforts to eliminate vision loss and improve quality of life through vision research, driving innovation and fostering collaboration to develop sight-saving treatments while expanding opportunities for people with vision impairment.
The research builds upon previous work published in Science Translational Medicine in 2019, which demonstrated the potential of clinical-grade stem cell-derived retinal pigment epithelium patches in rescuing retinal degeneration in animal models.
