Lab-grown "mini-eyes" unlock understanding of blindness, a rare genetic disease

Researchers at the Great Ormond Street Institute for Child Health (UCL GOS ICH) at University College London have developed "mini-eyes", which make it possible
to study and better understand the development of blindness in a rare genetic condition, Ushel syndrome.

The 3D 'mini-eyes', known as organoids, were grown from stem cells produced from skin samples donated by patients at Great Ormond Street Hospital for Children (GOSH
).
In healthy eyes, rod cells — a type of cell that detects light — are distributed in an important area
at the back of the eye called the retina that processes images.
In the study, published in Stem Cell Reports, the team found that they could allow rod-shaped cells to organize themselves into layers, mimicking tissue in the retina, creating a "mini-eye.
"
These "mini-eyes" are an important step forward, as previous studies using animal cells have not been able to mimic the same type of vision loss
seen in Arthur's syndrome.
Ushel syndrome is the most common genetic cause of deafness and blindness, affecting about 3 to 10 people per 100,000 people worldwide
.
Children with type 1 Usher syndrome are often born with severe deafness, and their vision slowly deteriorates until they become blind
in adulthood.
Although cochlear implants can help reduce hearing loss, there is currently no treatment
for retinitis pigmentosa.
Retinitis pigmentosa can cause vision loss
in people with Usher syndrome.
While the research is still in its early stages, these steps to understand the condition and design future treatments may offer hope
to those on the verge of blindness.

The "mini-eyes" developed in this study allow scientists to study the light-sensitive cells of the human eye at the 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 observe tiny molecular changes
before rod cells die.
Through this "mini-eye," the team found that Müller cells, which are responsible for retinal metabolic and structural support, are also linked
to Usher syndrome.
They found that people with Usher syndrome had abnormal stress response and protein-breaking genes
in their cells.
Reversing these may be key to
preventing disease progression and progression.

Because the "mini-eye" is grown from cells donated by patients who carry and do not carry "defects" in the genes that cause Arthur's syndrome, the team was able to compare healthy cells with cells that can cause
blindness.

Understanding these differences can provide clues
to understanding the changes that occur in a child's eyes before their vision begins to deteriorate.
This, in turn, can provide clues to the best targets for early treatment – which is critical
to delivering the best outcomes.

Dr Yeh Chwan Leong, associate researcher and first author at GOS ICH at University College London, said: "It is difficult to study the inaccessible tiny nerve cells in a patient's retina because they are so intricately connected and subtly located at the back of the
eye.
By doing a small biopsy of the skin, we now have the technology to reprogram cells into stem cells and then create lab-grown retinas with the same DNA as our patients, and therefore the same genetic conditions
.
While it will be some time away, we hope these models will help us one day develop treatments that will save the vision
of children and young adults with Usher syndrome.
”

The "mini-eye" model of ophthalmic diseases could also help the research team understand genetic disorders in which rod cells die in other eyes, such as retinitis pigmentosa
without deafness.
In addition, the technique used to grow reliable models of disease from human skin cells can be applied to many other diseases – an area
of expertise for the Zayed Centre for Rare Diseases in Children at University College London.

Future studies will create "mini-eyes" from more patient samples and use them to determine treatments, for example by testing different drugs
.
In the future, it will be possible to avoid blindness
by editing the DNA of specific cells in a patient's eye.

Molecular pathology of Usher 1B patient-derived retinal organoids at single cell resolution