Scientists from the Friedrich Miescher Institute (FMI) groups led by Botond Roska (pictured top) and Witold Filipowicz (pictured bottom) have resolved the mechanism controlling the maintenance of the light detectors – the cone photoreceptor outer segments – in the retina. With this knowledge, they have been able to induce the formation of functional photoreceptors in cultured retinas derived from embryonic stem cells. This opens up exciting new avenues for the study and treatment of blindness.
In about a third of all cases, loss of vision is caused by a loss of photoreceptor function. The most prevalent disease of this type – age-related macular degeneration (AMD) – is affecting a growing population of older adults. Others, such as retinitis pigmentosa or Stargardt disease, affect fewer but younger patients.
In recent years, therapeutic approaches using stem cells for retinal diseases such as AMD have gained a lot of attention. However, progress has been hampered by a lack of understanding of the molecular processes controlling the maintenance of cone photoreceptor outer segments – which serve as light detectors – and the inability to grow retinas with functional photoreceptors from stem cells.
Scientists led by Botond Roska (FMI Group leader) and Witold Filipowicz (FMI emeritus Group leader) have now successfully identified two small RNA molecules – both only approximately 20 nucleotides in length – necessary for the dynamic maintenance of the outer segments of cone photoreceptors in mice. In the absence of these microRNAs (miR-182 and miR-183), cone outer segments and cone vision is lost. Cone cells, one of the two types of photoreceptors present in the retina, are responsible for color vision and fine detail. The microRNAs thus control the maintenance of the retinal structures which are essential for the majority of our visual tasks. This research, reported in Neuron, started more than 5 years ago and was driven by Volker Busskamp and Jacek Krol – co-first authors of the paper – who are both postdoctoral fellows at FMI.
Most excitingly, miR-182 and miR-183 induced the formation of photoreceptor outer segments in cultured retinas derived from embryonic stem cells, generating responses to light.
Roska comments: “The understanding of the mechanisms leading to the formation and maintenance of outer segments – and thus functional photoreceptors – is highly valuable, as we can now derive functional retinas from stem cells under clearly defined conditions. The next step is to study the processes leading to the loss of outer segments in retinas derived from patients’ skin cells, and to find compounds that have an effect on these processes.”
Illustration: Friedrich Miescher Institute for Biomedical Research.
Friedrich Miescher Institute for Biomedical Research News Release (07/04/14)
Abstract (Neuron; 07/04/14))