Researchers find reprogrammed skin cells can treat blindness

Retinal cells grown in dishes, called photoreceptors, react in the same way as healthy retinal cells. (CREDIT: Creative Commons)

Retinal cells grown from stem cells can communicate with neighbors, completing a “handshake” that could indicate the cells are ready for testing in people with degenerative eye diseases, according to a new study.

More than a decade ago, researchers at the University of Wisconsin-Madison developed a way to grow organized clusters of cells called organelles that resemble the retina, the light-sensitive tissue at the back of the eye. They coaxed human skin cells, reprogrammed to act like stem cells, to develop into layers of several types of retinal cells that sense light and ultimately relay what we see to the brain.

“We wanted to use cells from these organoids as spare parts for the same types of cells that were lost during retinal diseases,” says David Gamm, professor of ophthalmology at the University of Washington at Madison and director of the MacPherson Eye Research Institute, whose laboratory developed the organoids. “But after several months of growing in a lab dish as compact clusters, the question remained – will the cells behave properly after we separate them? Because that’s the key to getting them into the patient’s eye.”

In 2022, Gamm and UW-Madison collaborators published studies showing that dish-grown retinal cells called photoreceptors respond in the same way as healthy retinal cells to different wavelengths and light intensities, and that once they separate from neighboring cells in their organelle, they can reach out to new neighbors with characteristic biological cords called axons.

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“The final piece of the puzzle was to see if these cords could connect or shake hands with other types of retinal cells to communicate,” says Gumm, whose new results on successful connections between cells will be published. this week in the Proceedings of the National Academy of Sciences.

Retinal and brain cells communicate through synapses, tiny gaps at the ends of their cords. To confirm that their lab-grown retinal cells had the ability to replace diseased cells and carry sensory information like healthy ones, the researchers needed to show that they could form synapses.

Xinyu Zhao, professor of neuroscience at the University of Washington at Madison and co-author of the new study, has been working with Gamm lab cells to help study their ability to form synaptic connections. They did this by using a modified rabies virus to identify pairs of cells that could form the means to communicate with each other.

Evidence for the presence of synapses connecting pairs of retinal cells derived from human pluripotent stem cells is the red coloration of infection with a modified rabies virus transmitted from one cell with a yellow nucleus through the synapse to a cell that glows only red. (TEACHER: UW-MADISON / GAMM LABORATORY)

The research team, including graduate students and co-authors Allison Ludwig and Stephen Mayerl, split retinal organoids into individual cells, gave them a week to lengthen their axons and make new connections, exposed them to the virus, and then took a look. What they saw was a plethora of retinal cells marked with a fluorescent color, indicating that the rabies infection had infected one through a synapse successfully formed between neighbors.

“We crafted this story together in the lab, bit by bit, to build confidence that we were moving in the right direction,” says Gumm, who patented the organoids and co-founded Opsis Therapeutics in Madison. which adapts technology for the treatment of human eye diseases based on the discoveries of UW-Madison. “All of this is ultimately leading to human clinical trials, which are the obvious next steps.”

David Gamm’s lab has developed a way to grow retinal-like organelles. (CREDIT: UW–MADISON)

Once they confirmed the presence of synaptic connections, the researchers analyzed the cells involved and found that the most common retinal cell types that form synapses were the rod and cone photoreceptors that are lost in diseases such as retinitis pigmentosa and age-related macular degeneration, and as well as some eye injuries. The next most common cell type, retinal ganglion cells, degenerate in diseases of the optic nerve such as glaucoma.

“It was an important revelation for us,” Gumm says. “This really shows the potentially wide impact that these retinal organelles can have.”

For more science news, visit our New Discoveries section at The bright side of the news.

Note: Materials provided above by the University of Wisconsin-Madison. Content can be edited for style and length.

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