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Three teams win NIH’s 3D Retinal Organoid Challenge

Winning teams create retinas-in-a-dish that will aid research, drug development
August 31, 2022
Fluorencent microscope image of retinal organoid colored in red, blue and green

Retinal organoid showing radial Muller glia and a well-organized outer layer consisting of photoreceptor cells.  Image credit: M. Natalia Vergara and M. Valeria Canto-Soler

Three scientific teams that developed physiologically competent retinal organoid systems have won the final phase of the 3D Retinal Organoid Challenge (3D ROC). The challenge, managed by the National Eye Institute (NEI) tasked researchers to recreate the complex cellular and neuronal circuitry of the retina in reproducible, outside-the-body systems that could serve as a platform for research and drug development. The three winning teams were led by Maria Valeria Canto-Soler, Ph.D. University of Colorado Anschultz Medical Campus, Aurora; Maria Natalia Vergara, Ph.D., University of Colorado Anschultz Medical Campus; and Wei Liu, Ph.D., Albert Einstein College of Medicine, New York City. NEI is part of the National Institutes of Health.

Fluorescent microscope image of retinal organoid with red and blue staining of columnar cells and green cells at the base.

3D retinal tissue complex derived from hiPSC that recreates the cellular composition of the outer retina. Image credit: M. Valeria Canto-Soler

“The retina is an amazingly complex tissue, with neuronal circuitry and layers of support cells that all interact to give us functional vision,” said Tom Greenwell, Ph.D., director of NEI’s Office of Regenerative Medicine. “This challenge was designed to help research teams develop new retina-in-a-dish research models that can be used to accelerate vision research and bring us closer to treatments for eye diseases. Organoids like those produced by our three winning teams are an exciting new tool in our research toolbox.”

3D ROC, launched in 2017, was designed in three phases. In the first phase, which closed September 2017, researchers presented conceptual frameworks for designing and building retinal organoids. In the second phase, which closed December 2020, researchers showed significant progress towards a functional retinal organoid. 

In the third and final phase, researchers designed retinal organoids that recapitulate the major cellular groups and functions of the living human retina, including light-sensing photoreceptors, supportive retinal pigment epithelial (RPE) cells, retinal ganglion cells, and vascular cells. Descriptions of the winning teams follow.

The team led by Canto-Soler, which won $500,000, created a retinal organoid system with functional photoreceptors and RPE cell layers, including most structures in what’s known as the “outer retina.” Inclusion of the RPE cell layer suggests this organoid can be used as a research model for age-related macular degeneration (AMD), a leading cause of blindness in American adults.

The team led by Vergara won $250,000 for development of a retinal organoid model that is highly reproducible, making it useful for high-throughput drug screening. 

Four images showing retinal organoids at different stages of development.

Retinal organoids at day 105 display a stratified structure, as demonstrated by amacrine cell marker PAX6, progenitor/bipolar cell marker VSX2, photoreceptor markers OTX2 and RCVN. (C, D) Retinal organoids at day 215 maintain a stratified structure and are rich in cones, as shown by cone marker OPN1MW/LW and rod marker RHO. Image credit: Wei Liu

The team led by Liu won $125,000 for developing a retinal organoid with all the major neuron groups in the retina. These organoids included an area with extra cone photoreceptors similar to the human fovea, the region of the retina that gives us high acuity central vision. These retinal organoids will be particularly useful for testing gene therapies affecting neuronal function. 

Finally, a team led by Robert J. Johnston Jr., Ph.D., Johns Hopkins University, Baltimore, received an honorable mention for their 3D ROC entry. The Johnston team created retinal organoids with a full complement of cone photoreceptor types and developed a new method to differentiate cone subtypes.


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Lesley Earl