Lab-grown 'mini eyes' shed light on blindness in rare genetic disease

Lab-grown ‘mini eyes’ shed light on blindness in rare genetic disease

Newswise – Researchers from the UCL Great Ormond Street Institute of Child Health (UCL GOS ICH) have developed ‘mini eyes’, which help to study and better understand the development of blindness in a rare genetic condition called Down syndrome. ‘Usher for the first time.

The 3D ‘mini-eyes’, known as organoids, were grown from stem cells generated from skin samples donated by patients at Great Ormond Street Hospital for Children (GOSH). In a healthy eye, rod cells – cells that detect light – are arranged at the back of the eye in an important image processing region called the retina. In this research published in Stem Cell Reports1the team found they could make the rod cells organize themselves into layers that mimic their organization in the retina, producing a ‘mini-eye’.

These “mini eyes” are a significant advance, as previous research using animal cells could not mimic the same type 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 in every 100,000 people worldwide. Children with Usher syndrome type 1 are often born profoundly deaf, while their sight slowly deteriorates until they become blind in adulthood.

Although cochlear implants can help with hearing loss, there is currently no treatment for retinitis pigmentosa, which causes vision loss in Usher syndrome. Although this research is still in its infancy, these steps towards understanding the disease and designing a future treatment could give hope to those who will lose their sight.

The “mini eyes” developed in this research allow scientists to study the light-sensitive cells of the human eye on an individual level, and in greater detail than ever before. For example, using powerful single-cell RNA sequencing, this is the first time researchers have been able to visualize the tiny molecular changes in rod cells before they die. Using ‘mini-eyes’, the team discovered that Müller cells, responsible for the metabolic and structural support of the retina, are also implicated in Usher syndrome. They found that the cells of people with Usher syndrome had abnormally activated genes for stress responses and protein breakdown. Reversing them could be the key to preventing disease progression and worsening.

Because the “mini-eyes” are grown from cells donated by patients with and without the genetic “fault” that causes Usher syndrome, the team can compare healthy cells and those that will lead to blindness.

Understanding these differences could provide clues to the changes that occur in the eye before a child’s vision begins to deteriorate. This, in turn, could provide clues to the best targets for early treatment – ​​essential for getting the best results.

Dr Yeh Chwan Leong, Research Associate at UCL GOS ICH and first author, said: “It is difficult to study the tiny, inaccessible nerve cells in the patient’s retina because they are so tightly bound and delicately positioned at the back of the eye. Using a small skin biopsy, we now have the technology to reprogram the cells into stem cells and then create a lab-grown retina with the same DNA, and therefore the same genetic conditions, as our patients.

Professor Jane Sowden, professor of developmental biology and genetics at UCL and lead author, said: “We are very grateful to the patients and families who donate these samples to research so that together we can deepen our understanding of genetic eye diseases, such as Usher syndrome.

Although they have been absent for some time, we hope that these models can one day help us develop treatments that could save the sight of children and young people with Usher syndrome.”

The “mini-eye” model for eye disease could also help teams understand other inherited conditions in which there is rod cell death in the eye, such as forms of retinitis pigmentosa without deafness. Additionally, the technology used to develop faithful disease models from human skin cells can 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 GOS ICH.

Future research will create ‘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 modify a patient’s DNA in specific cells in their eyes to prevent blindness.

This research was funded by the National Institute for Health and Care Research Center for Biomedical Research at Great Ormond Street Hospital, the Medical Research Council, GOSH Children’s Charity and Newlife the Charity for Disabled Children.

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