Lab-Grown Retinas to Restore Vision Are a Step Closer to Human Trials : ScienceAlert
Scientists from the University of Wisconsin-Madison in the US have induced light-sensitive eye cells grown in a laboratory to reconnect after division, 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 transforming light wavelengths into signals that the brain interprets as vision.
It has been a goal of researchers to grow retinal cells outside the body and use them to replace dead or dysfunctional tissue inside the eye.
In 2014, researchers generated organoids (clusters of cells self-organized into 3D shapes in the laboratory) that resembled the shape and function of a real retina. They did this by reprogramming human skin cells to act as stem cells, which were then encouraged to develop into certain types of retinal cells.
Last year, the same team published studies showing that lab-grown retinal cells can respond to different wavelengths and intensities of light, and reach out to neighboring cells to form connections.
According to lead ophthalmologist researcher David Gamm, this new study is “the final piece of the puzzle.”
“We wanted to use the cells from those organoids as replacement parts for the same types of cells that are lost during retinal diseases,” says Gamm.
“But after growing them in a lab dish for months as compact clusters, the question remained—will the cells behave properly once we separate them? Because that’s the key to getting them into the patient’s eye.”
This functionality depends on cells being able to connect to each other using extensions called axons, with a chemical signal box called a synapse forming a junction.
Seeing axons running between cells is one thing. To make sure that working connections were made, the team pulled out groups of retinal cells and watched them reconnect.
A rabies virus was then added, which was seen migrating between retinal cells over the course of a week, indicating that synaptic connections had indeed been formed.
Synapses connecting pairs of retinal cells derived from human pluripotent stem cells via a modified cell-to-cell rabies virus infection. (UW–Madison/Gamm Laboratory)
“We’ve been building this story together in the lab, one piece at a time, to build confidence that we’re going in the right direction,” says Gamm, of the University of Wisconsin-Madison.
“This is all leading, ultimately, to human clinical trials, which are the obvious next step.”
Further analysis revealed that the cell types that most frequently formed synapses were photoreceptors, commonly distinguished as rods and cones. This is encouraging because these types of cells are what 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 may be useful in treating disorders such as glaucoma, where the optic nerve that connects the eye to the brain is damaged.
“This was an important discovery for us,” says Gamm. “This really shows the potentially far-reaching impact that these retinal organoids can have.”
The research is published in PNAS.