Reprogrammed Skin Cells Can Treat Blindness

Retinal cells grown from stem cells can reach out and connect with neighbors, according to a new study, completing a “handshake” that may show the cells are ready for trials in humans with degenerative eye disordersOver a decade ago, researchers from the University of Wisconsin–Madison (UW-Madison) developed a way to grow organized clusters of cells, called organoids, that resemble the retina, the light-sensitive tissue at the back of the eye. They coaxed human skin cells reprogrammed to act as stem cells to develop into layers of several types of retinal cells that sense light and ultimately transmit what we see to the brain.

“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,” says David Gamm, the UW–Madison ophthalmology professor and director of the McPherson Eye Research Institute whose lab developed the organoids. “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.”

During 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, and that once they are separated from adjacent cells in their organoid, they can reach out toward new neighbors 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,” says Gamm, whose new results on successful connections between the cells will be published this week in the Proceedings of the National Academy of SciencesCells in the retina and brain communicate across synapses, tiny gaps at the tips of their cords. To confirm that their 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.

Source: https://news.wisc.edu/ 
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https://www.thebrighterside.news/

Stem Cells to Reverse Glaucoma

Retinal cells grown from stem cells can reach out and connect with neighbors, according to a new study, completing a “handshake” that may show the cells are ready for trials in humans with degenerative eye disorders.

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

Proof of synapses connecting pairs of retinal cells derived from human pluripotent stem cells comes from the red coloring of infection by a modified rabies virus passed from one cell with a yellow nucleus across the synapse to a cell that glows only red

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,” says David Gamm, the UW–Madison ophthalmology professor and director of the McPherson Eye Research Institute whose lab developed the organoids. “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.

During 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, and that once they are separated from adjacent cells in their organoid, they can reach out toward new neighbors 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,” says Gamm, whose new results on successful connections between the cells was published in the Proceedings of the National Academy of Sciences.

Source: https://news.wisc.edu/

How To Reverse Congenital Blindness

Researchers funded by the  American National Eye Institute (NEI) have reversed congenital blindness in mice by changing supportive cells in the retina called Müller glia into rod photoreceptors. The findings advance efforts toward regenerative therapies for blinding diseases such as age-related macular degeneration and retinitis pigmentosa. A report of the findings appears online today in Nature. NEI is part of the National Institutes of Health.

This is the first report of scientists reprogramming Müller glia to become functional in the mammalian ,” said Thomas N. Greenwell, Ph.D., NEI program director for retinal neuroscience. “Rods allow us to see in low light, but they may also help preserve cone photoreceptors, which are important for color vision and high visual acuity. Cones tend to die in later-stage eye diseases. If rods can be regenerated from inside the eye, this might be a strategy for treating diseases of the eye that affect photoreceptors.”

Photoreceptors are light-sensitive cells in the retina in the back of the eye that signal the brain when activated. In mammals, including and humans, photoreceptors fail to regenerate on their own. Like most neurons, once mature they don’t divide.

Scientists have long studied the regenerative potential of Müller glia because in other species, such as zebrafish, they divide in response to injury and can turn into photoreceptors and other retinal neurons. The zebrafish can thus regain vision after severe retinal injury. In the lab, however, scientists can coax mammalian Müller glia to behave more like they do in the fish. But it requires injuring the tissue.

From a practical standpoint, if you’re trying to regenerate the retina to restore a person’s vision, it is counterproductive to injure it first to activate the Müller glia,” said Bo Chen, Ph.D., associate professor of ophthalmology and director of the Ocular Stem Cell Program at the Icahn School of Medicine at Mount Sinai, New York.

We wanted to see if we could program Müller glia to become rod photoreceptors in a living mouse without having to injure its retina,” added Chen, the study’s lead investigator.

Source: https://www.nih.gov/
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https://medicalxpress.com/