NIH Tests Surgery to Boost Dry AMD Cell Therapy

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National Institutes of Health (NIH) scientists have developed a new surgical technique for implanting multiple tissue grafts in the eye's retina. The findings in animals may help advance treatment options for dry age-related macular degeneration (AMD), which is a leading cause of vision loss among older Americans. A report about the technique published today in JCI Insight.

In diseases such as AMD, the light-sensitive retina tissue at the back of the eye degenerates. Scientists are testing therapies for restoring damaged retinas with grafts of tissue grown in the lab from patient-derived stem cells. Until now, surgeons have only been able to place one graft in the retina, limiting the area that can be treated in patients, and as well as the ability to conduct side-by-side comparisons in animal models. Such comparisons are crucial for confirming that the tissue grafts are integrating with the retina and the underlying blood supply from a network of tiny blood vessels known as the choriocapillaris.

For the technique, investigators designed a new surgical clamp that maintains eye pressure during the insertion of two tissue patches in immediate succession while minimizing damage to the surrounding tissue.

In animal models, the scientists used their newly designed surgical technique to compare two different grafts placed sequentially in the same experimentally induced AMD-like lesion. One graft consisted of retinal pigment epithelial (RPE) cells grown on a biodegradable scaffold. RPE cells support and nourish the retina's light-sensing photoreceptors. In AMD, vision loss occurs alongside the loss of RPE cells and photoreceptors. In the lab, RPE cells are grown from human blood cells after they've been converted into stem cells. The second graft consisted of just the biodegradable scaffold to serve as a control.

Post surgery, scientists used artificial intelligence to analyze retinal images and compare the effects of each graft. They observed that the RPE grafts promoted the survival of photoreceptors, while photoreceptors near scaffold-only grafts died at a much higher rate. Additionally, they were able to confirm for the first time that the RPE graft also regenerated the choriocapillaris, which supplies the retina with oxygen and nutrients.

The findings expand on the capability demonstrated in an ongoing, NIH-led first-in-human clinical trial of patient-derived RPE grafts for the dry form of AMD.

The work was supported by the National Eye Institute Intramural Research Program

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