Retinal cells grown from stem cells can reach out and connect with neighbours, researchers in the US have learned.
The discovery, by the University of Wisconsin–Madison, could lead to a new treatment for blindness.
More than a decade ago, researchers at the university developed a way to grow organised clusters of cells, called organoids, that resemble the retina.
David Gamm, the UW–Madison ophthalmology professor and director of the McPherson Eye Research Institute whose lab developed the organoids, said:
“We wanted to use the cells from those organoids as replacement parts for the same types of cells that have been lost in the course of retinal diseases.
“But after being grown in a laboratory dish for months as compact clusters, the question remained — will the cells behave appropriately after we tease them apart? Because that is key to introducing them into a patient’s eye.”
In 2022, Gamm and UW–Madison collaborators published studies showing that dish-grown retinal cells called photoreceptors respond like those in a healthy retina to different wavelengths and intensities of light.
Once the cells are separated from adjacent cells in their organoid, they can reach out toward new neighbours with characteristic biological cords called axons.
“The last piece of the puzzle was to see if these cords had the ability to plug into, or shake hands with, other retinal cell types in order to communicate,” Gamm added.
Cells within the retina and brain communicate across synapses – tiny gaps at the tips of their cords.
To confirm that the lab-grown retinal cells have the capacity to replace diseased cells and carry sensory information like healthy ones, the researchers needed to show that they could make synapses.
UW–Madison professor of neuroscience Xinyu Zhao worked with the Gamm lab’s cells to help study their ability to form synaptic connections.
The researchers did this using a modified rabies virus to identify pairs of cells that could form the means to communicate with one another.
The research team broke apart the retinal organoids into individual cells, gave them a week to extend their axons and make new connections, exposed them to the virus, and then had a look.
The team saw that many retinal cells marked by a fluorescent colour indicating a rabies infection had infected one across a synapse successfully formed between neighbours.
Gamm said:
“We’ve been quilting this story together in the lab, one piece at a time, to build confidence that we’re headed in the right direction.
“It’s all leading, ultimately, to human clinical trials, which are the clear next step.”
The researchers then analysed the cells involved and found that the most common retinal cell types forming synapses were photoreceptors lost in diseases like retinitis pigmentosa and age-related macular degeneration, as well as in certain eye injuries.
The next most common cell type, retinal ganglion cells, are degenerate in optic nerve disorders like glaucoma, which affects more than 3 million people in the US alone.
Gamm said:
“That was an important revelation for us.
“It really shows the potentially broad impact these retinal organoids could have.”
