Scientists have taken a significant step towards developing new treatments for blindness after successfully restoring retinal function in mice using lab-grown cells.
Researchers at Duke University in North Carolina used induced pluripotent stem cells (iPSCs) to grow specialised retinal blood vessel cells, which were then injected into mice with retinal disease. The cells integrated into damaged tissue, regenerated blood vessels and restored retinal function, including in a model of diabetic retinopathy, one of the leading causes of vision loss among working-age adults.
The findings, published in the journal Nature Biomedical Engineering, mark the first time researchers have successfully generated these specialised retinal blood vessel cells from human stem cells.
Induced pluripotent stem cells are adult cells that have been reprogrammed into stem cells capable of developing into almost any type of cell in the body. The technology was pioneered by Japanese scientist Shinya Yamanaka, who was awarded the 2012 Nobel Prize in Physiology or Medicine for the breakthrough.
Professor Sharon Gerecht, who led the study, said the research could pave the way for new therapies for retinal diseases that affect millions of people worldwide.
"Retinal vascular diseases affect millions of people, but our understanding remains limited, hindering our ability to discover and develop new therapeutics," Gerecht said.
"Using human stem cells, we generated the cells found in retinal blood vessels, paving the way for new therapeutic approaches."
The retina, located at the back of the eye, is an extension of the central nervous system and is protected by a specialised blood-retinal barrier that regulates the movement of oxygen, nutrients and other substances.
While this barrier helps protect the eye, it also makes retinal diseases difficult to treat.
"When this specialised blood vessel tissue begins to break down, it can cause a lot of different diseases that lead to vision loss," said Parker Esswein, a PhD student and co-author of the study.
Current retinal endothelial cells used for research are typically obtained from human donors, making them expensive and difficult to source. The Duke team sought to overcome these limitations by producing a reliable supply of the cells from stem cells.
Researchers first transformed commercially available stem cells into general endothelial cells before using a specialised mixture of growth factors to convert them into retinal endothelial cells.
Laboratory tests showed the cells formed the same complex blood vessel networks found in healthy retinal tissue.
The team then exposed the engineered tissue to low oxygen and high glucose levels, conditions that mimic diabetic retinopathy. The lab-grown tissue responded in much the same way as human retinal tissue, with the protective barrier breaking down.
In a further breakthrough, the researchers injected the lab-grown cells into mice before significant vision loss had occurred. The cells successfully integrated into the retina, strengthened blood vessels and restored the integrity of the protective barrier.
"The tests showed that these lab-grown cells have promise for preventative treatments, especially since they should be easier and cheaper to obtain using our technique," Esswein said.
Although the study focused on animal models, researchers believe the technology could also provide a powerful platform for studying human eye diseases and testing new treatments before they reach clinical trials.
The research team is now exploring additional applications for the stem cell-derived retinal cells through laboratory studies and partnerships with industry. A patent has also been filed covering the technology for both potential stem cell therapies and laboratory models used in drug discovery and testing.
While further research and human clinical trials will be required before the treatment becomes available to patients, the findings represent a promising advance in the search for therapies that could one day restore sight to people affected by blinding retinal diseases.