University of Toronto researchers develop cell injection technology to help reverse vision loss-Edexlive

Researchers have developed a new method of injecting healthy cells into damaged eyes. This technique can show the path to new treatments that could reverse the form of blindness that is currently untreatable.

A study led by an engineering researcher at the University of Toronto is published in Biomaterials. Around the world, there are millions of people living blind and blind due to conditions such as age-related macular degeneration (AMD) and retinitis pigmentosa. Both are caused by the death of retinal cells in the back of the eye.

“The cells responsible for visual acuity are the photoreceptors, which have a close relationship with another type of cell known as the retinal pigment epithelium (RPE) cells,” says Molly Shoiche.

“In AMD, RPE dies first, which in turn kills photoreceptors.”

Many researchers have tried treatments that inject healthy photoreceptors or RPE cells into the eye to replace dead cells. However, integrating new cells into existing tissue is a major challenge, and most injected cells will die as well.

Shoichet and her team are experts who use artificial biomaterials called hydrogels to promote the survival of newly injected cells after transplantation. Hydrogels ensure a uniform distribution of cells, reduce inflammation and promote healing of important early tissues after injection. Eventually it decomposes naturally, leaving healthy cells.

In 2015, the team used hydrogels to inject healthy photoreceptors into the damaged retina of a mouse model. The team observed some vision repairs, but the benefits were limited, so they began to think more carefully about the relationship between RPE cells and photoreceptors.

“The RPE and photoreceptors are considered one functional unit. If one cell type dies, the other will die,” Shoichet says. “I wondered if simultaneous delivery of both cell types would have a significant impact on vision recovery.”

As with photoreceptors, many groups have tried to transplant RPE cells themselves, but no one has combined both cell types into a single treatment. Once again, the hydrogel pointed to the solution.

“What the other group usually does is injecting the photoreceptors with saline, which allows cells to cluster together or to form a layer of RPE cells, usually grown on a polymer film. It’s surgically implanted,” says Shoichet.

“Our hydrogel is viscous enough to ensure good distribution of both cell types within the syringe, but with a significant shear reduction that facilitates the very fine needle injection required for this procedure. It also has viscous properties,” Shoichet adds. “The combination of these properties has opened up new strategies for successful delivery of multiple cells.”

The team tested co-injection in a modified mouse model similar to AMD. Recently, a paper published in Biomaterials reported that co-injected mice recovered about 10% of normal vision. Little improvement was seen in patients who received either cell type alone.

Co-injected mice were also more active in the dark chamber than in the light chamber, indicating that these nocturnal animals can again distinguish between light and shadow.

“I still remember the long days of behavioral testing,” says Nick Mitrousis, a former PhD student at Shoichet, the lead author of the paper, and now a postdoctoral fellow at the University of Chicago.

“I designed the experiment so that I didn’t know which mice were treated and which received a placebo. When some mice started responding, I was optimistic that the experiment might actually work. I was agitated and worried that it would recover. The mice might just be divided into different treatment groups.”

The worries were unfounded: The coinjection treatment turned out to be really effective. However, both Mitrousis and Shoichet warn that there is a very long road between these preliminary results and the trials that may eventually find the way to the clinic.

“First, we need to demonstrate the benefits of this strategy in multiple animal models,” said Scheiche. “We also need a source of human photoreceptors that we are working on and ways to further improve cell survival. Nevertheless, we are very excited about these data and continue our research. You can always work together to help.”