Researchers in the US are developing lab-grown pig retinal organoids as part of a strategy to combat retinal disease in humans.
Organoids are small-tissue clusters – about the size of a large pin head – made up of hundreds of thousands of cells, which allow scientists to replicate the cellular interactions and conditions in a human tissue or organ, but in the controlled environment of a lab dish.
Inside the human eye, the retina is made up of several types of cells, including the light-sensing photoreceptors that initiate the cascade of events that lead to vision. Damage to the photoreceptors, either through degenerative disease or injury, leads to permanent vision impairment or blindness.
The challenge is that stem cell treatments aimed at replacing photoreceptors need to first be tested in animals. Since human cells are not compatible in other species and are quickly rejected when transplanted, it’s difficult to assess their potential.
Dr David Gamm, director of the University of Wisconsin–Madison’s McPherson Eye Research Institute and professor of ophthalmology and visual sciences, said pig and human retinas shared many key features, making pigs ideal for modelling human retinal disease and testing ocular therapeutics.
“By testing ‘human-equivalent’ photoreceptors in pigs, we can get a better sense of what these cells can do if they are not immediately attacked by the host animal.”
In a new study published in Stem Cell Reports, the Gamm Lab partnered with researchers at the Morgridge Institute for Research to develop lab-grown pig retinal organoids.
“This is the first time that people have made pig retinal organoids,” says Ms Kim Edwards, a graduate student in the Gamm Lab and first author of the study. “And this was the first time that people have done a comparison of human versus another species of retinal organoids.”
“The photoreceptor cells within human organoids can respond to light and communicate with each other through synaptic connections,” says Dr Gamm. “To determine whether they can connect inside a damaged retina and restore vision, we need to transplant and test them in pigs.”
After successfully generating pig-induced pluripotent stem cells, the next challenge was to encourage them to differentiate into retinal cells.
Edwards began by using the Gamm Lab’s established human organoid protocol to see if it would work using stem cells from pig. The protocol timing was based on the human gestation period of 40 weeks, but they noted a pig’s pregnancy is only about half that length. So, the scientists thought, what if we use the same protocol, but cut the timing in half?
“We were able to make a lot of retinal organoids from that, which was really exciting,” Edwards says. “It’s a good proof of concept to show that if we’re going to differentiate to a specific cell type, we really need to pay attention to the gestational differences and the inherent differences between the cells.”
More reading
Glaucoma stem cell research could help develop new drugs to combat disease
Glaucoma Australia ‘Quinlivan’ research grants open
The future of glaucoma detection and monitoring
