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Photoreceptors and retinal pigment epithelial (RPE) cells are key candidates for transplantation therapy of retinal disease, said James Bainbridge PhD, FRCOphth at the 14th EURETINA Congress in London.

Dr Bainbridge, of Moorfields Eye Hospital and the UCL Institute of Ophthalmology, discussed the recent results of early clinical trials using RPE cell transplantation.

His work focuses on transplanting RPE cells derived from human embryonic stem cells (hES-RPE) into the eyes of patients with end-stage Stargardt Disease, an early-onset hereditary macular dystrophy characterised by decreased central vision and atrophy of the macula. It is the most common form of juvenile macular degeneration, and is associated with mutations in ABCA4 and ELOVL4, resulting in RPE dysfunction and subsequent loss of photoreceptors.

“These pluripotent cells can be matured in the laboratory into RPE cells. Donor hES-RPE cells can survive in the mouse, and can protect retinal function,” said Dr Bainbridge.

RPE cells have been derived from both induced pluripotent stem cells and embryonic stem cells, the latter of which can provide an unlimited source. It has been clearly demonstrated that transplanted cells can provide anatomical and functional photoreceptor rescue in animal models.

After transplantation, survival of human embryonic stem cell-derived RPE cells can be proven via fluorescent staining with antibodies directed against human cellular structures, while protection of retinal function can be demonstrated via b-wave amplitude of a mouse electroretinogram.

Dr Bainbridge and his team are working with Ocata Therapeutics (previously Advanced Cell Technology) on a clinical trial to assess the safety of the procedure in humans. Twelve patients with Stargardt Disease have been included in four sequential cohorts of three subjects. Each cohort received a single subretinal injection of 50,000, 100,000, 150,000 or 200,000 hES-RPE cells suspended in 0.15ml medium. Immunosuppression was achieved with three months of tacrolimus/mycophenolate treatment. “The rationale is to promote photoreceptor survival and function by replenishing degenerate RPE with functioning RPE,” said Dr Bainbridge.

Retinal progeny derived from either pluripotent stem cells or tissue-specific retinal and RPE stem cells have the potential capacity both to replace damaged retina and to provide trophic support that might slow disease progression.

“The process faces many challenges,” said Dr Bainbridge. “The first among these is safety, which encompasses potential immunogenicity as well as the potential tumorgenicity of cells that retain some potential for proliferation. Patients must also be able to tolerate the three-month immunosuppression.”

Current results indicate that the procedure is safe in the short-term, as there have been no significant ocular or systemic adverse effects to date in this study. Although functional improvement has not yet been observed, this was not an expectation and may not be anticipated given the advanced stage of the disease of the eyes included in the study.

James Bainbridge:

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