News / Science News

    Researchers rescue photoreceptors, prevent blindness in animal models of retinal degeneration

    Using a novel patient-specific stem cell-based therapy, researchers at the National Eye Institute (NEI) prevented blindness in animal models of geographic atrophy, the advanced "dry" form of age-related macular degeneration (AMD).



    The researchers will take a patient’s own blood cells, and in a lab, convert them into iPS cells capable of becoming any type of cell in the body. The iPS cells are then programmed to become retinal pigment epithelial cells, the type of cell that dies early in the geographic atrophy form of AMD. Photo: NEI


    The therapy involves taking a patient’s blood cells and, in a lab, converting them into iPS cells, which can become any type of cell in the body. The iPS cells are programmed to become retinal pigment epithelial cells, the type of cell that dies early in the geographic atrophy stage of macular degeneration. RPE cells nurture photoreceptors, the light-sensing cells in the retina.

    In geographic atrophy, once RPE cells die, photoreceptors eventually also die, resulting in blindness. The therapy is an attempt to shore up the health of remaining photoreceptors by replacing dying RPE with iPSC-derived RPE.

    Before they are transplanted, the iPSC-derived RPE are grown in tiny sheets one cell thick, replicating their natural structure within the eye. This monolayer of iPSC-derived RPE is grown on a biodegradable scaffold designed to promote the integration of the cells within the retina. A specially designed surgical tool was built for the task of inserting the patch of cells between the RPE and the photoreceptors.

    Ten weeks after the human iPSC-derived RPE patches were implanted in the animals’ retinas, imaging studies confirmed that the lab-made cells had integrated within the animal retina.

    The investigators report the transplanted cells functioned properly. Immunostaining confirmed that the iPSC-derived RPE expressed the gene RPE65, suggesting the lab-made cells had reached a crucial stage of maturity necessary to maintain photoreceptor health. RPE65 is necessary for the regeneration of visual pigment within the photoreceptors and is an essential component for vision.

    Further tests showed that the transplanted RPE cells were pruning photoreceptors via phagocytosis, another RPE function that helps keep photoreceptors healthy. In addition, electrical responses recorded from photoreceptors rescued by RPE patches were normal; whereas photoreceptors treated with a control empty scaffold had died.

    A key concern with any stem cell therapy is its oncogenic potential: the ability for cells to multiply uncontrollably and form tumors. The researchers genetically analyzed the iPSC-derived RPE cells and found no genetic mutations linked to tumor growth. (National Institutes of Health)

    JANUARY 18, 2019



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