Producing Retinal Cells to Treat Blindness

Age-related macular degeneration is the most common cause of blindness in the elderly. This loss of vision is caused by the death of rods and cones resulting from the degeneration and death of the underlying RPE cells, which provide the rods and cones vital nourishment. In a study published today in Nature Communications, researchers found specific markers on the surface of the RPE cells that can be used to isolate and purify these retinal cells.

“The finding has enabled us to develop a robust protocol that ensures that the differentiation of embryonic stem cells into RPE cells is effective and that there is no contamination of other cell types,” says senior author Fredrik Lanner of the Karolinska institute. “We’ve now begun the production of RPE cells in accordance with our new protocol for the first clinical study, which is planned for the coming years.”

One obstacle when transplanting tissue generated from stem cells is the risk of rejection, which occurs if transplantation antigens of the donor and patient tissue differ. Research groups around the world are therefore working on creating what are known as universal cells, which ideally will not trigger an immune response.

In a study published in Stem Cell Reports the same group created embryonic stem cells that are able to hide from the immune system. Using CRISPR/Cas9 gene editing, they removed certain molecules—HLA class I and class II—which sit on the surface of the stem cells as a means by which the immune system can identify them as endogenous or not. The stem cells lacking these molecules were then differentiated into RPE cells.

The researchers have been able to show that the modified RPE cells retain their character, that no harmful mutations appear in the process, and that the cells can avoid the immune system’s T cells without activating other immune cells. The rejection response was also significantly smaller and more delayed than after the transplantation of regular RPE cells, the surfaces of which still possess HLA molecules.

“The research is still in an early stage, but this can be an important initial step towards creating universal RPE cells for the future treatment of age-related macular degeneration,” says co–senior author Anders Kvanta, also of the Karolinska Institute.