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Stories/From Our Labs

Science pic: Reprogramming a retina

By
Eric Bender
Jul 16, 2015

A bio-engineered three-dimensional model of the human retina.
Image: Arnaud Lacoste/Novartis

This colorful structure is a bioengineered three-dimensional model of the human retina. In this “organoid,” the green layer of cells is the retinal pigment epithelium, which nourishes retinal visual cells. The purple layer of cells gives rise to retinal ganglion cells—the nerves that connect the retina to the brain. Cells in all the other layers of the retina are shown in blue.

But what’s most striking about the image is that the model “was created entirely in a dish using a technology called cellular reprogramming, which lets us think about drug discovery in ways that we did not believe were possible five or six years ago,” says Arnaud Lacoste, an investigator in Ophthalmology at the Novartis Institutes for BioMedical Research.

The organoids start as a skin cell or blood cell obtained from a patient, Lacoste explains. He and his colleagues genetically reprogram that cell into an induced pluripotent stem cell, which can be differentiated into almost any cell in the body.

“We can generate the cell type that is affected in a patient’s disease, and the cell carries the very mutation that makes a patient sick,” Lacoste emphasizes. “This helps us understand very complex aspects of human diseases.”

Understanding the retina, one of the most complex organs in the human body, has long been a challenge. “Every single cell layer in the retina must be organized in a particular way to enable normal vision,” he points out. “When one or more of these layers degenerates, a patient can become blind.”

The retinal organoids replicate many of these structural features. “More work is required to make these organoids 100% identical to a retina but they are already helping to reveal how retinal cells develop, interact and function,” Lacoste says. “We can also see how specific compounds or genetic variations affect them.” While it’s early days for this project, the reprogramming approach should generate and culture the organoids at very large scales, allowing high-volume drug screening.

Among his team’s disease targets is Usher syndrome, a rare genetic disorder in which young people gradually lose both vision and hearing. “We have made organoids from patients who have Usher’s syndrome, and we are comparing them to organoids made from people who don’t have any disease,” Lacoste says. “We hope these will help us to understand what goes bad in the disease and how we can address the problem.”

Tags: 
Biomedical Research, Novartis Institutes for BioMedical Research, New Scientific Discoveries, Eye Disorders

Eric Bender

Eric Bender

has written about science ranging in scale from RNA to the outer heliosphere. During his spare time, he messes about in boats (in the summer) and shovels (in the winter).

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