From iPSC to RPE to Therapy

For patients with advanced dry AMD, a long-awaited treatment may be on the horizon. Researchers at the USA’s National Eye Institute (NEI) have successfully rescued retinal degeneration in rodent and pig models through cell-based therapy.

Kapil Bharti, Head of the NEI Unit on Ocular and Stem Cell Translational Research, led the investigation. He explains how the team used Nobel-Prize winning technology to pave the way for therapeutic success: “The blood cells are reprogramed using proteins that induce the expression of iPS cell genes. Within three weeks, blood cells start becoming iPS cells, where they are then expanded and used for making RPE.”

These iPS cell-derived RPE cells are grown on a biodegradable scaffold, designed to promote the integration of the cells within the retina. Once matured, the cells are inserted between the RPE and the photoreceptors, using a purpose-built surgical tool. There, they rescue photoreceptors that would otherwise die in geographic atrophy – the late state of dry AMD.

So how long does the process take? “It takes 10 weeks – all in all – to make functional RPE cells from iPS cells. Once transplanted, the cells start affecting vision within a few weeks,” says Bharti

The team ran tests to confirm that the transplanted cells expressed RPE65 – the gene necessary for the regeneration of photoreceptors and an essential component for vision. The tests also showed that the RPE cells were pruning photoreceptors via phagocytosis – another RPE function that keeps photoreceptors healthy.

Importantly, the team also took special measures to develop oncogenic mutation-free clinical-grade iPSCs to increase the safety of the treatment. And because the approach is autologous, the chances of rejection are virtually non-existent.

Bharti and his team are planning to start a phase I trial later in 2019.