The retina is the part of the eye that receives and organizes visual information. It contains millions of light-sensitive cells and nerves and consists of five different layers that together send signals to the brain. While the structure of the retina is well known, researchers have so far hardly been able to examine the complex structure in practice. “The desire was therefore to develop a model retina that is very similar to the real organ,” says Cameron Cowan from the Institute for Molecular and Clinical Ophthalmology Basel (IOB).
And that is exactly what Cowan’s researchers have now achieved: To do this, they used pluripotent stem cells that they cultivated on a nutrient medium to form five-layer organoids – that is, to form an artificial retina. The mature organoids reacted to light on their surface layers and transmitted visual impulses to the cell layers inside via their synapses – as happens in the eye.
During the genetic analysis of the organoids, the team found that their transcriptomes – i.e. all gene products produced – stabilized after maturation. And even in the long term: the organoids contained most of the gene products of the retinal cell types for up to 38 weeks. The IOB researchers then compared the organoids with the human retinas from organ donors. The comparison showed that the cell-specific transcriptomes in maturing organoids become increasingly similar to those in the natural retina over time. From this, the researchers developed an overview of the cell types of the artificial and real retina for the first time and created a publicly accessible list of the transcriptomes for each retinal cell type.
According to the researchers, this is also a valuable advance for the treatment of eye diseases: “You can cultivate high-quality retinal organoids that are obtained from a patient’s own pluripotent stem cells,” says Cowan’s colleague Magdalena Renner. “And with the transcriptome atlas you can find out where a disease gene is being expressed.” In the future, gene therapies tailored to individual patients could be developed.