Newswise – Researchers at UCL Great Ormond Street Institute of Child Health (UCL GOS ICH) have grown ‘mini-eyes’, which make it possible to study and better understand the development of blindness in a rare genetic disease called Usher syndrome For the first time.
The 3D ‘mini-eyes’, known as organoids, were grown from stem cells generated from skin samples donated by patients at the Great Ormond Street Hospital for Children (GOSH). In a healthy eye, rod cells — the cells that sense light — are located in the back of the eye in an important area responsible for processing images, the retina. In this research, published in Stem cell reports1the team found they could get rod cells to organize themselves into layers that mimic their organization in the retina, creating a “mini-eye.”
These ‘mini-eyes’ are an important step forward, as previous research using animal cells was unable to replicate the same kind of vision loss seen in Usher syndrome.
Usher syndrome is the most common genetic cause of combined deafness and blindness, affecting approximately three to ten out of every 100,000 people worldwide. Children with type 1 Usher syndrome are often born deaf, with their vision slowly deteriorating until they are blind in adulthood.
While cochlear implants can help with hearing loss, there are currently no treatments for retinitis pigmentosa, which causes vision loss in Usher syndrome. While this research is in its early stages, these steps to understanding the condition and designing future treatment may give hope to those who will lose their vision.
The ‘mini-eyes’ developed in this research allow scientists to study light-sensitive cells of the human eye at an individual level, in greater detail than ever before. For example, using powerful single-cell RNA sequencing, it’s the first time researchers can see the tiny molecular changes in rod cells before they die. Using the ‘mini-eyes’, the team discovered that Müller cells, responsible for the metabolic and structural support of the retina, are also involved in Usher’s syndrome. They found that cells from people with Usher syndrome have abnormal genes that are turned on for stress responses and protein breakdown. Reversing this could be the key to preventing the disease from progressing and worsening.
Because the ‘mini eyes’ are grown from cells donated by patients with and without the genetic ‘flaw’ that causes Usher syndrome, the team can compare healthy cells to cells that will lead to blindness.
Understanding these differences can provide clues to changes in the eye before a child’s vision begins to deteriorate. This, in turn, could provide clues to the best targets for early treatment – crucial for the best outcome.
Dr Yeh Chwan Leong, Research Associate at UCL CIS ICH and first author said: “It is difficult to study the inaccessible small nerve cells of the patient’s retina because they are so intricately interconnected and delicately positioned at the back of the eye. By using a small biopsy of the 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 the same genetic disorders, as our patients.”
Professor Jane Sowden, Professor of Developmental Biology and Genetics at UCL, and senior author, said: “We are deeply grateful to patients and families who donate these samples for research so that together we can advance our understanding of genetic eye disorders such as Usher syndrome.
While it will take some time, we hope that these models can one day help us develop treatments that can save the sight of children and young people with Usher Syndrome.”
The ‘mini-eye’ model of eye disease could also help teams understand other inherited conditions in which rod cells die in the eye, such as forms of retinitis pigmentosa without deafness. In addition, the technology used to grow faithful disease models from human skin cells could be used for a number of other diseases – this is an area of expertise of the Zayed Center for Research into Rare Disease in Children at UCL CIS ICH.
Future research will take ‘mini-eyes’ 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 into specific cells in their eyes to prevent blindness.
This research was funded by the National Institute for Health and Care Research Great Ormond Street Hospital Biomedical Research Center, Medical Research Council, GOSH Children’s Charity and Newlife the Charity for Disabled Children.