Researchers simulate Usher syndrome in retinal organoids

Retinal organoids grown in a dish have shed light on the mechanisms behind a genetically-inherited cause of blindness called Usher syndrome.

A team of researchers from University College London Great Ormond Street Institute of Child Health was able to convert skin cells of patients with Usher syndrome into organoids that modelled the retina, the part of the eye at the back which is responsible for light detection. Induced pluripotent stem cells were also used to create retinal organoids of unaffected individuals to use as a control. These organoids were found to display the different retinal cells and accurately mimicked their interactions.

'These retinas in a dish really help us to see what is going on at the back of the eye, which is important for Usher syndrome and in future could potentially help to develop treatments for more complicated problems like age-related macular degeneration', project leader Professor Jane Sowden told the Daily Mail.

The retina captures and translates visual inputs, making them accessible to the brain which allows us to see. Inherited retinal dystrophies (IRD) affect one in 2000 people worldwide. These patients generally have a suboptimal visual experience, noticing blind spots in their visual field, difficulty with depth perception and poor contrast sensitivity, among others. Usher syndrome is a type of IRD that is also accompanied by hearing loss, being the most frequent genetic cause of deaf blindness.

Although more than 300 genes are known to cause IRD, the mechanisms by which they give rise to disease are not yet identified in many of them. In their recent paper published in Stem Cell Reports, Professor Sowden's team reports that retinal photoreceptors (specialised light-sensitive cells) from patients with Usher syndrome exhibited overexpression of genes associated with cellular stress responses. They also found that retinal Muller cells, responsible for metabolic and structural support of the retina but not previously associated with Usher's mechanism, were affected by the disease.

These organoids have allowed investigation into a condition that was difficult to replicate in animal models, researchers said.

'Being able to use mini-eyes is a breakthrough in the field, which many scientific teams are working on. I believe that in ten years many cases of inherited blindness will be reversible', said Professor Sowden.