Health
Lab-grown eye cells form new neural connections
overview
- Ocular cells grown from skin-derived stem cells can be harvested from 3D culture and induced to form new neural connections.
- These results highlight the potential of using transplanted cells to restore vision.
In degenerative eye diseases such as retinitis pigmentosa, macular degeneration, and glaucoma, eye cells begin to die. These cells capture light and send visual information to the brain. Their loss can eventually lead to vision loss and blindness.
When eye cells die, the body cannot regenerate them. Researchers have been studying whether replacement eye cells can be grown in the lab and transplanted into the eye to restore vision. For such strategies to work, replacement cells must be able to form communication links with existing cells called synapses.
A research team led by Dr. David Gamm at the University of Wisconsin-Madison has been experimenting with growing human eye cells in culture. In previous work, they showed that stem cells derived from human skin cells can be reprogrammed to generate structures called retinal organoids. Organoids contain many types of cells that the eye needs to see. These include rod and cone photoreceptors, which sense light, and retinal ganglion cells, which send information to the brain.
To restore vision, cultured cells implanted in the eye must form new synapses. However, it has not been shown whether organoid cells can be harvested to create new synapses.
In a new study, Gamm and his colleagues tested this problem using tracer molecules that can traverse the connections made by individual neurons.Their results will be announced on January 10, 2023. Proceedings of the National Academy of Sciences.
The team first grew the retinal organoids for 80 days, giving several different types of eye cells time to mature.
All pre-existing synaptic connections were disrupted during organoid disassembly. But 20 days after the researcher isolated individual cells, all cell types were once again able to produce the proteins needed to form new synapses.
To track whether these isolated cells can form synaptic connections, the team cultured the cells with a rabies virus-based tracer. The rabies virus travels from neuron to neuron through synapses. By combining a harmless version of the virus with a fluorescent tracer, the team was able to track the virus through new synaptic connections.
Using tracers, researchers found that cells were forming new synaptic connections. In the new neural circuit, several types of eye cells were discovered. Photoreceptors were the most common, followed by retinal ganglion cells.
“The final piece of the puzzle,” Gann says. [cells] It had the ability to connect or shake hands with other retinal cell types in order to communicate. Now that this ability has been proven, the team is working to adapt the technology to treat human eye disease.
— Sharon Reynolds
Funding: NIH’s National Eye Institute (NEI), National Institute of Mental Health (NIMH), and Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Department of Defense; Fighting Blindness in Canada; Research to Prevent Blindness; Foundation for Retina Research; Emmett A. Humble Distinguished Directorship; McPherson ERI Sandra Lemke Trout Chair in Eye Research; Dean’s Office, University of Wisconsin-Madison School of Veterinary Medicine; UW-Madison Center for Stem Cell and Regenerative Medicine. Foundation Fighting Blindness.
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