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Gilbert Bernier
Credit: ResearchGate
Scientists at Université de Montréal have successfully transplanted retinas made from stem cells into blind mini-pigs – and, it seems, made them see again, according to a new study.
Published today in the British biological journal Development, the research led UdeM neurosciences professor Gilbert Bernier shows potential for treating retinal degenerative diseases in humans, as well.
“To get as close as possible to human clinical application, we chose mini-pigs because the size of their eyes is near that of humans and the animals are about the same weight as humans,” said Bernier.
“Hence, all surgeries in our study could be performed by a retinal surgeon.”
In their stem cell and developmental biology laboratory of the UdeM-affilated Maisonneuve-Rosemont Hospital, Bernier and his team developed a method to coax stem cells into forming sheets of cells that recapitulate the structure of the human retina.
The type of stem cells they used are called human induced pluripotent stem cells – immature cells ‘reprogrammed’ from an adult (mature) cell that can differentiate into any type of cells in the body. Using the stem cells, the researchers made ‘retinal sheets’ that are enriched in immature versions of the cone photoreceptor cells, which could become mature cone cells when cultured in the lab.
After successfully creating the retinal sheets in a dish, the researchers tackled the next challenge: transplanting these sheets into mini-pigs with damaged macula. Once that was done, they found that the retinal grafts were able to integrate into the mini-pig’s damaged retinal tissue.
The mini-pigs showed signs of restored vision: new neural connections were formed between the grafted photoreceptor cells and the minipigs’ neural cells, and the scientists could detect neural activity of the photoreceptors at the grafted area when the mini-pigs were placed in a well-lit room.
Millions of people are affected by retinal degenerative diseases. In most cases, loss of vision is caused by damage to the macula, a region in the centre of the retina. The macula is rich in cone photoreceptors – cells important for perceiving colour and seeing finer details. Today there are no approved treatments to replace the damaged macula.
Given the pressing need to develop therapeutic interventions against vision loss, researchers around the world are testing different ways to repair damaged macula.
“Some approaches use dissociated photoreceptor cells; others create micro-dissected retinal organoids, which are lab-grown ‘mini- organs’ in a dish,” said Bernier. “In contrast, our method allows the spontaneous formation of a flat retinal tissue that is already polarised and organised, as in the human embryonic retina,”and can generate large yields of retinal tissue for transplantation.
A limitation in this method lies in the difficulty of controlling the placement and orientation of the grafts during surgery. The macula is only four millimetres in diameter – about the length of a grain of rice. “To properly orient, place and stabilise the graft in the retina remains a big surgical challenge,” said Bernier.
His team are now working to improve the transplantation success rate. They are validating an experimental retinal surgery device to ensure proper orientation and implantation of the graft at the correct retinal disease site.