Restoring eyesight with genetically engineered stem cells

Eye
Mesenchymal stem cells from bone marrow have properties that could help retinal cells repair themselves. (Unsplash)

Several diseases are marked by retinal degeneration that eventually leads to blindness, including age-related macular degeneration (AMD) and retinitis pigmentosa. Targeting these diseases with gene and cell therapies is a popular pursuit, though picking the right targets has proven challenging.

Researchers at the Centre for Genomic Regulation (CRG) in Barcelona are developing a stem cell treatment for retinal degeneration that focuses on two chemokine receptors, Ccr5 and Cxcr6, which they identified to be important players in cell signaling. They engineered mesenchymal stem cells from bone marrow to have an excessive amount of Ccr5 and Cxcr6 and transplanted them into models of retinal degeneration. That preserved the function of degenerating retinal tissue, they reported in the journal Molecular Therapy.

Scientists who study eye diseases have long known that stem cells have properties that could help retinal cells repair themselves. They release molecules that protect neural cells and tamp down inflammation, for example. But using stem cells to treat eye diseases is challenging, because the cells struggle to migrate to the eye and integrate into the retina, explained lead author and CRG research professor Pia Cosma in a statement.

“After the cells are transplanted they need to reach the retina and integrate through its layers,” Cosma said. “Here we have found a way to enhance this process using stem cells commonly found in the bone marrow, but in principle can be used with any transplanted cells.”

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Mesenchymal stem cells could offer several advantages for the treatment of eye diseases, including an ability to differentiate into retinal cells and to be grown outside the body, the CRG researchers noted. They reported that when their altered cells were transplanted into models of human and mouse retinal diseases, the cells migrated in high numbers to deteriorating retinal tissue and prevented the death of retinal cells.

Other research groups are investigating a variety of cell therapies for treating eye diseases. Earlier this year, a team led by the National Institutes of Health’s National Eye Institute described a technique for transforming skin cells into rod photoreceptors and then implanting them into mouse models of retinal degeneration.

A Mount Sinai team is working on a therapy that involves stimulating and then genetically reprogramming dormant Müller glial cells in the retina to repair damage. Researchers at the University of Southern California made a retinal implant from embryonic stem cells and showed in a small clinical trial that it could improve sight in people with advanced dry AMD.

The next step for the CRG team is to investigate whether alternative cell-modification methods might improve their Ccr5- and Cxcr6-targeted therapy. They modified the stem cells for their study with lentiviruses, which have been used in experimental gene therapies. But adeno-associated virus vectors, which have gained regulatory approvals for use in gene and cell therapies, could also be modified to express the two chemokine receptors, the researchers said.