Lab-Grown Eye Yields New Insights into Usher Syndrome

Researchers in London have used lab-grown “mini eyes” to better understand Usher Syndrome, a rare genetic disease that causes blindness. The 3-D organoids were grown from stem cells generated from skin samples donated by patients at Great Ormond Street Hospital for Children (GOSH) and more accurately mimic the mechanisms underlying Usher Syndrome sight loss than previous work using animal cells.

Usher syndrome is the most common genetic cause of combined deafness and blindness, affecting approximately three to ten in 100,000 people worldwide. Children with Type 1 Usher syndrome are often born profoundly deaf, while their sight slowly deteriorates until they are blind by adulthood. Although cochlear implants can help with hearing loss, there are currently no treatments for retinitis pigmentosa, which causes vision loss in Usher syndrome.

Because the organoids developed in this work are grown from cells donated by patients with and without the genetic fault that causes Usher syndrome, comparisons can be made between healthy cells and those that will lead to blindness. Understanding these differences could provide clues to changes that happen in the eye before a child’s vision begins to deteriorate. In turn, this could provide clues to the best targets for early treatment.

In a healthy eye, light-detecting rod cells are arranged in the retina, located in the back of the eye. The authors of the study found that they could get rod cells to organize themselves into layers that mimic their organization in the retina, producing the “mini eye.”  The organoids allowed the team to study light-sensing cells from the human eye at an individual level, and in more detail than ever before.

“It’s difficult to study the inaccessible tiny nerve cells of the patient’s retina as they are so intricately connected and delicately positioned at the back of the eye,” says Dr. Yeh Chwan Leong, Research Associate at University College London’s GOS and first author of the study. “By using a small biopsy of skin, we now have the technology to reprogram the cells into stem cells and then create lab-grown retina with the same DNA, and therefore same genetic conditions, as our patients.”

The team was able to use the organoids to discover that Müller cells, which are responsible for metabolic and structural support of the retina, are also involved in Usher syndrome. They found that cells from people with Usher syndrome abnormally have genes turned on for stress responses and protein breakdown. Reversing these could be the key to preventing how the disease progresses and worsens.

The model for eye diseases could also help teams understand other inherited conditions in which there is the death of rod cells in the eye, such as forms of retinitis pigmentosa without deafness.

Future research will create organoids from more patient samples and use them to identify treatments, for example by testing different drugs. In the future, it may be possible to edit a patient’s DNA in specific cells in their eyes to avoid blindness.

Additional details  can be found in a recent issue of the journal Stem Cell Reports.