Stem cells could hold the key to a future therapy for age-related macular degeneration (AMD), the leading cause of sight-loss among older adults.
The disease leads to the loss of retinal photoreceptor cells, the light-sensitive elements that convert light into nerve signals the brain can understand. This robs patients of their central, or macula, vision, the most acute part of the retina which is used to read, watch television or recognise peoples' faces.
Part of the pathology involves the degeneration of a tissue layer called the retinal pigment epithelium, a sheet of melanin-containing cells that nourish and maintain the photoreceptors. Replacing this lost tissue could therefore help to retard the progression of the condition.
To do this, Maria Kokkinaki and her colleagues at Georgetown University in Washington DC, writing in the journal Stem Cells, have developed a technique to transform mature skin cells into these specialised retinal cells. First the skin cells are "reprogrammed" by adding four genes (OCT4, SOX2, NANOG AND LIN28) which wipe the genetic slate of the cells and convert them into stem cells called hiPS cells (human induced pluripotential stem cells).
Grown under the correct culture environment, the team have found, these hiPS can be converted into retinal pigment epithelial cells that show identical morphology, gene activity, electrical, structural and biochemical behaviours to their naturally-encountered counterparts.
Crucially, once re-specialised, the cells showed no markers associated with still being stem cells, which is important from a safety perspective. This suggests that it should be possible to produce retinal spare-parts to tackle some of the commoner sight-loss syndromes using a similar technique.
However, the cells weren't perfect though. The telomeres, structures resembling end-caps on the chromosomes which shorten when cells divide, were shorter than they should have been, and the cells also showed other damage to their DNA which the team suspects might have been caused by the viruses used to deliver the reprogramming genes at the start of the procedure. This indicates that the technique, whilst an important proof of principle, has some way to go before it is ready for the clinic.
As study co-author Nady Golestaneh puts it, "This isn't ready for prime time though. We also identified some issues that need to be worked out before these cells are ready for transplantation but overall, this is a tremendous step forward in regenerative medicine."