Scientists at the University of Wisconsin-Madison in the United States have persuaded light-sensitive eye cells grown in the laboratory to reconnect after separation, an important step for transplantation into patients to treat various eye diseases.
Working together, these photoreceptor cells combine with other cells to form the retina; a thin layer of tissue at the back of the eye responsible for translating wavelengths of light into signals that the brain interprets as vision.
The researchers’ goal was to grow retinal cells outside the body and use them to replace dead or dysfunctional tissue inside the eye.
In 2014, researchers generated organoids (self-organized groups of cells into 3D shapes in the lab) that resembled the shape and function of a real retina. They did this by reprogramming human skin cells to act like stem cells, which were then encouraged to develop into several types of retinal cells.
Last year, the same team published studies showing that retinal cells grown in the lab can respond to different wavelengths and intensities of light, as well as reach out to neighboring cells to make connections.
According to lead research ophthalmologist David Gamm, this new study is “the final piece of the puzzle”.
“We wanted to use the cells from these organoids as spares for the same types of cells that have been lost in retinal diseases,” Gamm says.
“But after being grown in a lab dish for months as tight clusters, the question remained: will the cells behave correctly after you separate them? Because that’s the key to getting them into the eye. of a patient.”
This functionality depends on the ability of cells to connect to each other using extensions called axons, with a chemical signal box called a synapse forming a junction.
Seeing axons stretch between cells is one thing. To make sure that functional connections had been made, the team separated groups of retinal cells and watched them reconnect.
A rabies virus was then added, which was seen to migrate between retinal cells over the course of a week, indicating that synaptic connections had indeed been established.
“We’ve been quilting this story together in the lab, one piece at a time, to build confidence that we’re headed in the right direction,” says Gamm, of the University of Wisconsin-Madison.
“All of this leads, ultimately, to human clinical trials, which are clearly the next step.”
Further analysis revealed that the cell types that most commonly formed synapses were photoreceptors, generally distinguished into rods and cones. This is encouraging, because these types of cells are the ones that are lost in diseases such as retinitis pigmentosa and age-related macular degeneration.
There was also evidence of cell types called retinal ganglion cells forming synapses. Replacing these cells in the eye could be useful in treating conditions such as glaucoma, where the optic nerve connecting the eye to the brain is damaged.
“It was an important revelation for us,” says Gamm. “It really shows the potentially broad impact that these retinal organoids could have.”
The research has been published in PNAS.