© J. Gopalakrishnan
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Human-induced pluripotent stem cells (HiPSCs) can be used to generate brain organoids that have an ocular structure.

Organoids are fragments of organ tissue grown from stem cells. 3D human brain organoids derived from induced pluripotent stem cells present unprecedented opportunities for studying the complexity of brain development and diseases.

This has also been demonstrated by research carried out at the Heinrich Heine Universität in Düsseldorf, Germany. A team led by Jay Gopalakrishnan has shown that organoids spontaneously developed bilaterally symmetrical optical heads at the front of the brain-like part of the organoid. This indicates that IPSCs are capable of self-assembling themselves within a highly complex biological process.

Retinal diseases

These organoids can help in studying brain-eye interactions during embryonic development, in modeling congenital retinal disorders, and in generating patient-specific retinal cell types for the testing of personalized drugs and transplantation therapies.

“Our work further highlights the remarkable ability of brain organoids to generate primitive sensory structures that are sensitive to light and have cell types similar to those found in the body,” Jay Gopalakrishnan said in a press release. He is a professor at the Faculty of Medicine at the Heinrich Heine Universität in Düsseldorf and the lead author of the study.

Optical cups

Gopalakrishnan and his team adapted a protocol they had previously developed for converting HiPSCs into neural tissue. The human brain organoids formed optical cups that appeared after 30 days and grew into visible structures within 50 days. This time frame corresponds to the development of the retina in the human embryo.

The researchers generated 314 brain organoids, 72 percent of which formed optic nerve heads, thus showing that the method is reproducible. These structures comprised several types of retinal cells that formed electrically active neuronal networks responsive to light. The brain organoids also contained lens and corneal tissue and showed a connection between the retina and the brain regions.

Eye nerve

In future studies, the researchers hope to develop strategies to keep the optic nerve heads alive for long periods of time and use them to study the mechanisms that cause retinal diseases. The study was published this week in the journal Cell Stem Cell (Elsevier).

Read how the Heinrich Heine Universität is also leading the way in purifying surface water here.