A lab-grown cell treatment has restored retinal function in mice, in a step that researchers at Duke University say could open new options for eye disease treatment and research.

Biomedical engineers at the North Carolina university used induced pluripotent stem cells, or iPSCs, to grow retinal endothelial cells, specialised blood vessel cells that are critical to retinal health, for the first time.

When the cells were injected into mouse models of retinal disease, they integrated into damaged tissue to regenerate blood vessels and restore retinal function, according to the team’s study in Nature Biomedical Engineering.

The researchers also showed the cells could form functional retinal vascular tissue in a lab-grown setting, which they said could help model and study eye diseases.

Study leader Sharon Gerecht said: “Retinal vascular diseases affect millions of people, but our understanding remains limited, hindering our ability to discover and develop new therapeutics.

“Using human stem cells, we generated the cells found in retinal blood vessels, paving the way for new therapeutic approaches.”

Gerecht said the retina, the back part of the eye that detects light, is directly linked to the brain because its neurons extend to it. She said the retina also has a blood barrier that tightly controls what passes in and out, including oxygen, nutrients, water and pharmaceuticals.

She said: “This barrier is formed by blood vessel tissue comprising a tight network of retinal endothelial cells, which form the inner layer of blood vessels, in concert with other specialized cells called pericytes and astrocytes.

“The specificity of these cells and the fact that they do not form in other areas of the body make the complex tissue difficult to heal or to grow from scratch.”

First co-author Parker Esswein, a PhD student in the Gerecht lab, said breakdown of this specialised blood vessel tissue can drive diseases linked to vision loss.

He said: “When this specialized blood vessel tissue begins to break down, it can cause a lot of different diseases that lead to vision loss.

“While there are sources of retinal endothelial cells, being able to grow a continuous supply from scratch could offer many advantages for those working in the field.”

Retinal endothelial cells are currently collected and grown from patients, which the researchers said makes them expensive and limited in supply.

To expand access, reduce cost and control variability, the team started with commercial iPSCs, which are mature adult cells reprogrammed into an earlier state so they can develop into other cell types. They first grew them into common endothelial cells, then used a cocktail of growth factors to turn them into the retinal form.

In experiments, the cells formed the same networks and structures seen in the body. The team then exposed the lab-grown tissues to low oxygen and high glucose levels, conditions they said are fundamental triggers of diabetic retinopathy, the leading cause of vision loss in working-age people in the United States.

Those conditions caused the tissue barrier to break down in the lab model, the researchers said, as it does in patients.

The team then tested the cells as a treatment in mouse models with weak, unstructured retinal blood vessels. When injected before any vision loss occurred, the cells integrated into the existing tissue and helped build strong blood vessels with strong barriers.

Esswein said: “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.”

He added: “While our benchtop experiments did not attempt to model a wide variety of specific eye diseases in these studies, we’re confident we can create excellent human tissue models in the lab to help better understand these diseases and uncover therapies.”

The team said it is now exploring potential uses for the retinal endothelial cells in the lab and through industry partnerships. It also has a patent pending covering the stem cell-based therapeutics and in vitro modelling for drug discovery and testing.

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