Bioprinted Eye Tissue to Study Retinal Diseases

Researchers at the National Eye Institute, which is part of the National Institutes of Health, have created a method to 3D bioprint eye tissue that forms the outer blood-retina barrier. This tissue supports the photoreceptors in the retina and is implicated in the initiation of age-related macular degeneration.

The outer blood-retina barrier is the interface of the retina and the choroid, including Bruch’s membrane and the choriocapillaris. Image credit: National Eye Institute.

The researchers combined different cell types, which are primarily derived from patient stem cells, in a hydrogel carrier that is suitable for bioprinting and created a tissue structure that mimics many of the features of the native tissue. The researchers hope that the technique will allow them to create an unlimited supply of eye tissue with which to study various eye diseases.

Researchers are making strides in developing more advanced in vitro tissue models to study disease. Many diseases lack relevant and useful in vitro models and in many cases experimental animals may not accurately mimic human physiology, as well as entailing ethical concerns. Therefore, there is a need to develop more advanced in vitro systems that allow us to accurately mimic human tissues and study disease.

 

The eye’s outer blood-retina barrier comprises retinal pigment epithelium, Bruch’s membrane and the choriocapillaris. Image credit: National Eye Institute. 

“We know that age-related macular degeneration starts in the outer blood-retina barrier,” said Kapil Bharti, a researcher involved in the study. “However, mechanisms of age-related macular degeneration initiation and progression to advanced dry and wet stages remain poorly understood due to the lack of physiologically relevant human models.”

To address this, these researchers developed a 3D bioprinted model of the outer blood-retina barrier. In age-related macular degeneration, the retinal pigment epithelium (RPE) of this tissue breaks down, leading to photoreceptor degeneration and eventual vision impairment.

To create the printed constructs, the researchers combined three cell types, which had been derived from patient stem cells. These were pericytes, endothelial cells, and fibroblasts. They mixed the cells with a temperature sensitive hydrogel and then bioprinted the mixture onto a biodegradable scaffold.

Growth of blood vessels across printed rows of an endothelial-pericyte-fibroblast cell mixture. By day 7, blood vessels fill in the space between the rows, forming a network of capillaries. Image credit: Kapil Bharti.

The researchers cultured the tissue constructs and observed that they reached maturity about six weeks later, demonstrating features of the native outer blood-retina barrier. They were then able to model age-related macular degeneration by exposing the tissue to low oxygen and they tested the effects of drugs that are used to treat the condition in humans.

“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, 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.”

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