DÜSSELDORF, Germany — “Mini brains” which scientists grow from human stem cells help researchers learn about how people grow from tiny embryos. Now, these brain organoids may also uncover how eye diseases form after an experiment revealed that these structures can grow their own eyes!
Using human induced pluripotent stem cells (iPSCs), researchers in Germany created brain organoids that contained their own eye structures called optic cups. These mini brains developed a pair of symmetrical optic structures right in the front of the brain-like region — just like a normal human baby would in the womb.
“Our work highlights the remarkable ability of brain organoids to generate primitive sensory structures that are light sensitive and harbor cell types similar to those found in the body,” says senior study author Jay Gopalakrishnan of University Hospital Düsseldorf in a media release. “These organoids can help to study brain-eye interactions during embryo development, model congenital retinal disorders, and generate patient-specific retinal cell types for personalized drug testing and transplantation therapies.”
Eyes in mini brains actually see the light
Pluripotent stem cells go on to become all types of cells in the body. Study authors say that 3D brain organoids help them examine human brain development and the diseases that form in this region. Moreover, they also teach scientists about how the brain connects to our vision through various nerves.
This isn’t the first time embryonic stem cells have developed their own optic cups. In fact, the process of making brain organoids gives rise to the development of a retina — the light-sensitive tissue layer on the back of a normal eye. Previous studies have also shown that optic cups can be produced by iPSCs taken from adult cells that scientists “reprogram” back into being embryonic stem cells again.
Previously, optic cups grown by pluripotent stem cell brains come from experiments attempting to create a pure retina. Unlike this new experiment, those cups did not fully integrate into their brain organoids.
Studying eye diseases from the ground up
To achieve this new breakthrough in stem cell development, Gopalakrishnan and his team changed the protocol for turning iPSCs into neural tissue. Doing so allowed the brain organoids to form their own optic cups. These cups appeared in about 30 days and matured into visible eye structures within 50 days. This mirrors actual retinal development in human embryos during pregnancy.
Overall, the team used 16 independent batches of cells from four iPSC donors, generating a total of 314 mini brains. From this group, 72 percent grew their own optic cups.
What makes these cups so special for scientists is that they each contain diverse retinal cell types. These cells form electrically active neuronal connections that respond to light, just like your own eyes do. The optic cups also had their own lens, corneal tissue, and displayed retinal connectivity to the mini brain region.
Having live lab models which grow “eyes” just like a human child would opens up the possibility that scientists can find the cause and triggers for retinal disorders which cause vision impairment and blindness.
“In the mammalian brain, nerve fibers of retinal ganglion cells reach out to connect with their brain targets, an aspect that has never before been shown in an in vitro system,” Gopalakrishnan concludes.
The study appears in the journal Cell Stem Cell.