THE ESSENTIAL
- Cells in the retina communicate through synapses, tiny spaces at the end of their cords where nerve messages are transmitted.
- In order to confirm that their retinal cells grown in the laboratory could indeed replace the diseased cells, the authors of the study had to show that they could manufacture synapses.
- “We are going in the right direction. All of this leads, ultimately, to human clinical trials, which are clearly the next step,” rejoices Professor Gamn.
Age-related macular degeneration, glaucoma… several diseases affecting the eye can lead to loss of vision. Unfortunately, modern medicine offers few treatment options once blindness sets in. However, researchers at the University of Wisconsin-Madison (UW-M) in the United States have made a stem cell discovery that could finally lead to a cure for degenerative eye diseases.
Scientists have succeeded in demonstrating that retinal cells derived from stem cells are able to “connect” by “joining hands” with their neighboring cells. Their new study was published on January 4, 2022 in the Proceedings of the US National Academy of Sciences (PNAS).
Skin cells reprogrammed to replace those of the retina
More than a decade ago, UW-Madison researchers developed a way to grow organized clumps of cells (organoids), which resemble the retina – a light-sensitive tissue at the back of the eye. Scientists then reprogrammed human skin cells to act as stem cells and grow into layers of many types of retinal cells that detect light, ultimately transmitting what we see to our brain.
“We wanted to use the cells from these organoids as spares for the same types of cells that have been lost in retinal diseases”explains David Gamm, professor of ophthalmology at UW-Madison and director of the McPherson Eye Research Institute whose laboratory developed the organoids, in a university statement.
According to studies the professor published last year, box-grown retinal cells, called photoreceptors, react like those in a healthy retina to different wavelengths and light intensities. After being separated from adjacent cells in their organoid, they can then connect to their new neighbors thanks to characteristic biological cords, the axons. “The final piece of the puzzle was to see if these cords had the ability to plug into, or ‘shake hands with’ other types of retinal cells in order to communicate”adds David Gamm.
“It was an important revelation for us”
Xinyu Zhao, professor of neuroscience at UW-Madison and co-author of the study, worked with the cells in the Gamm lab to study their ability to form synaptic connections. Zhao achieved this by using a modified rabies virus capable of identifying pairs of cells that could form the means necessary to communicate with each other.
After the team confirmed the presence of synaptic connections, the research team discovered, after analysis, that the most common types of retinal cells forming synapses were photoreceptors (rods and cones). A remarkable discovery because photoreceptors are generally lost in diseases such as age-related macular degeneration, retinitis pigmentosa or certain eye lesions. The second most common cell type (ganglion cells) degenerates in optic nerve disorders like glaucoma. “It was an important revelation for usconcludes Professor Gamm. It really shows the potentially broad impact that these retinal organoids could have.”
