3D-bioprinted eye tissue will help researchers understand blinding diseases

They used a hydrogel to mix three immature choroidal cell types.
Nergis Firtina
3D printed eye tissue.
3D printed eye tissue.

NIH/YouTube 

Researchers from the National Eye Institute used 3D bioprinting to create eye tissue that will help them understand the mechanisms of blinding diseases.

Under the National Health Institute, NEI reserachers printed a combination of cells that form the outer blood-retina barrier—eye tissue that supports the retina's light-sensing photoreceptors. The method makes it possible to research age-related macular degeneration and other degenerative retinal illnesses using a theoretically limitless supply of patient-derived tissue (AMD), according to the press release.

"We know that AMD starts in the outer blood-retina barrier," said Kapil Bharti, Ph.D., who heads the NEI Section on Ocular and Stem Cell Translational Research. "However, mechanisms of AMD initiation and progression to advanced dry and wet stages remain poorly understood due to the lack of physiologically relevant human models." 

How was the process?

Bharti and colleagues used a hydrogel to mix three immature choroidal cell types: pericytes and endothelial cells, which are important components of capillaries, and fibroblasts, which give tissues structure. The gel was then printed on a biodegradable scaffold by the scientists. The cells began to grow into a dense capillary network within days.

On the ninth day, the researchers implanted cells from the retinal pigment epithelium on the other side of the scaffold. On day 42, the printed tissue was fully developed. 

According to tissue investigations, genetic tests, and functional analysis, the printed tissue resembled the natural outer blood-retina barrier in appearance and behavior. Under conditions of generated stress, printed tissue displayed early AMD characteristics, such as drusen deposits beneath the RPE, and advanced to late dry-stage AMD, where tissue deterioration was seen. 

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Low oxygen levels caused a wet AMD-like look with choroidal vascular hyperproliferation that moved into the sub-RPE zone. When used to treat AMD, anti-VEGF medications slowed the formation and migration of blood vessels while also improving tissue shape.

"By printing cells, we're facilitating the exchange of cellular cues that are necessary for normal outer blood-retina barrier anatomy," said Bharti. "For example, the presence of RPE cells induces gene expression changes in fibroblasts that contribute to the formation of Bruch's membrane – something that was suggested many years ago but wasn't proven until our model."

3D-bioprinted eye tissue will help researchers understand blinding diseases
Growth of blood vessels across printed rows of an endothelial-pericyte-fibroblast cell mixture.

NIH 

Biofabricated "in-a-well"

The blood-retina barrier tissues were biofabricated "in-a-well" by co-author Marc Ferrer, Ph.D., director of the 3D Tissue Bioprinting Laboratory at the National Center for Advancing Translational Sciences of the National Institutes of Health.

"Our collaborative efforts have resulted in very relevant retina tissue models of degenerative eye diseases," Ferrer said. "Such tissue models have many potential uses in translational applications, including therapeutics development."

To further mimic genuine tissue, Bharti and colleagues are experimenting with adding additional cell types to the printing process, such as immune cells. These models of the blood-retina barrier will be used to study AMD.

The study was published in Nature on December 23.

Study abstract:

We engineered a 3D outer-blood-retina-barrier (3D-oBRB) with a fully polarized retinal pigment epithelium (RPE) monolayer on top of a Bruch's membrane and a fenestrated choriocapillaris network. This 3D-oBRB tissue faithfully recapitulates RPE– choriocapillaris interactions, dry age-related macular degeneration (AMD) phenotypes (including sub-RPE drusen deposits and choriocapillaris degeneration) and the wet AMD phenotype of choriocapillaris neovascularization.

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