"PNAS" artificial retinal cells successfully connected to the eye! Unlock a host of new treatments for eye diseases

According to a new study, retinal cells grown from stem cells can reach out to connect with neighbors, completing a "handshake," which could indicate that the cells are ready
for trials in patients with degenerative eye disease.

More than a decade ago, researchers at the University of Wisconsin-Madison developed a way to grow organized clusters of cells called organoids, similar to the retina, photosensitive tissue
at the back of the eye.
They induced human skin cells to reprogram to act as stem cells, developing into layers of several types of retinal cells that sense light and eventually transmit what we see to the brain
.

"We wanted to use these organoid cells as replacement parts of the allocells lost during retinal disease," said David Gamm, a professor of ophthalmology at the University of Wisconsin-Madison and director of the McPherson Eye Institute, whose lab developed the organoids
.
"But after a few months of culture in a lab dish, the question remained—after we isolated the cells, did they behave normally?" Because this is the key
to introducing them into the patient's eyes.
”

During 2022, Gamm and collaborators at the University of Wisconsin-Madison published a study showing that retinal cells grown in discs called photoreceptors, like cells in healthy retinas, respond to light of different wavelengths and intensities, and once they are isolated from neighboring cells in organoids, they can reach out to new neighbors
with characteristic biocords called axons.

"The final puzzle is to see if these wires have the ability to insert or shake hands with other types of retinal cells to communicate
," Gamm said.
His new results on successful connections between cells will be published
this week in PNAS.

Cells in the retina and brain communicate through synapses, tiny gaps
in nerve endings.
To confirm that the retinal cells grown in their lab have the ability to replace diseased cells and carry sensory information just like healthy cells, the researchers needed to show that they could make synapses
.

Xinyu Zhao, a professor of neuroscience at the University of Wisconsin-Madison and co-author of the new study, worked with cells in Gamm's lab to help study their ability to
form synaptic connections.
They used a modified rabies virus to identify pairs
of cells that can form ways to communicate with each other.

The team, which included graduate students and co-first authors Allison Ludwig and Steven Mayerl, broke down retinal organoids into individual cells, gave them a week to lengthen axons and make new connections, exposed them to the virus, and then observed
.
What they saw were many fluorescent-colored retinal cells, suggesting that rabies virus infection had infected synapses
that had successfully formed between neighboring cells.

"We've been putting this story together in the lab, one at a time, to build confidence that we're moving in the right direction," said Gamm, who patented organoids and co-founded Madison's Opsis Therapeutics, which is adopting the technology to treat human eye diseases
based on findings from the University of Wisconsin-Madison.
"It's all going to eventually move towards human clinical trials, which is the definitive next step
.
"

After they confirmed the presence of synaptic connections, the researchers analyzed the cells in question and found that the most common types of retinal cells that form synapses are photoreceptors — rod cells and conical cells — that are lost
in diseases such as retinitis pigmentosa and age-related macular degeneration, as well as certain eye injuries.
The second most common cell type, retinal ganglion cells, degenerative optic nerve diseases such as glaucoma
.

Gamm said: "This is an important revelation
for us.
This does indicate the potentially wide-ranging effects
that these retinal organoids can have.
”