STEM CELL RESEARCH

STEM CELL RESEARCH

After successful “proof of principle” trials in animal models, researchers are hopeful that stem cell technology can be successfully used in the near future to reverse photoreceptor loss in humans with advanced retinal disease, according to a presentation at the 13th EURETINA Congress in Hamburg.

“There is a lot of exciting research in this field at the moment and the results from the early experiments in animal models are very encouraging. However, we do need to urge caution for our patients and bear in mind that more studies will be needed to establish the safety and efficacy of using stem cells for retinal repair in humans,” Mandeep Singh FRCSEd told delegates at the first ever symposium of the Young European Retinal Specialist Group held during the EURETINA meeting.

 

Most Beneficial

Dr Singh, a vitreoretinal Fellow at Oxford Eye Hospital, UK, and a researcher at the Nuffield Laboratory of Ophthalmology at the University of Oxford, said that stem cells could be potentially most beneficial when used in late-stage retinal disease such as advanced age-related macular degeneration and severe retinitis pigmentosa.

“Stem cells really fit into the replacement paradigm for treatment. In early-stage disease, the photoreceptor cells are still present, so gene therapy can be used to target the photoreceptors and make them functional again. In late-stage disease, however, when there are no photoreceptor cells present, the approach has to focus on replacement of the photoreceptors and perhaps the retinal pigment epithelium as well,” he said.

The concept that adult tissues – including the retina – could be generated through stem cell technology was demonstrated by the cloning of Dolly the sheep using somatic cell nuclear transfer in 1996, said Dr Singh.

Another key breakthrough came in 2006 when Robert MacLaren et al succeeded in transplanting photoreceptors directly into the eyes of mice and restored their visual function. The study found that transplanted photoreceptor precursor cells survived and became integrated into the mouse retina. Crucial to the success of the technique was the fact that the cells were isolated when they had reached a certain level of maturity.

Progress has accelerated since then, said Dr Singh, citing his 2013 study performed in Prof MacLaren's laboratory showing that the entire light-sensitive layer could be reconstructed in mice with a complete lack of light-sensing photoreceptor cells in their retinas.

 

Restoring Vision

Rather than placing discrete photoreceptors among pre-existing host outer retinal cells, Dr Singh’s study paves the way to total photoreceptor layer reconstruction as a potentially viable means of restoring vision.

Dr Singh said that many current research efforts are focused on using induced pluripotent stem cells (iPSC) as a potential limitless source of cells for transplantation. iPS cells can be generated directly from adult cells without
the need for embryos and can be propagated indefinitely.

A pilot study to assess the safety and feasibility of the transplantation of iPSC-derived retinal pigment epithelium (RPE) cell sheets in patients with exudative age-related macular degeneration has started at Dr Masayo Takahashi’s laboratory
in Japan.

 

Mandeep Singh: enquiries@eye.ox.ac.uk

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