24 August 2021

Organoids with eyes

Human induced pluripotent stem cells (iPSCs) have been used to generate brain organoids containing so–called eye glasses - the embryonic structure from which the human eye is subsequently formed. Organoids spontaneously developed symmetrical eye glasses from two sides from the anterior part of the brain-like region, demonstrating the ability of iPSCs to self-organize in a very complex biological process.

The work of Jay Gopalakrishnan and his colleagues from the University Hospital of Dusseldorf shows the amazing ability of brain organoids to generate primitive light-sensitive structures that contain cell types similar to those in the body. Such organoids can be useful for studying brain-eye interactions during embryo development, modeling congenital retinal abnormalities, and generating patient-specific retinal cell types for personalized drug testing and transplant therapy.

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Many aspects of human brain development and diseases can be studied using 3D brain organoids derived from pluripotent stem cells, which can give rise to all types of cells in the body. Researchers have previously grown eyeglasses from human embryonic stem cells, which give rise to the retina, the light–sensitive tissue in the back of the eye. But then the work was aimed only at the isolated creation of the retina. Until now, other three-dimensional structures of the eye have not been functionally integrated into brain organoids.

In their study, Gopalakrishnan and his group modified a protocol that they had previously developed to convert iPSCs into nerve tissue. The organoids of the human brain formed eye glasses after 30 days, which matured into visible structures within 60 days. These time frames correspond to the stages of eye development in the human embryo.

In 16 independent sets of iPSCs obtained from four donors, the researchers produced 314 brain organoids, 72% of which formed eye glasses, showing that the method is reproducible. These structures contained various types of retinal cells that formed active neurons that respond to light. In addition to the retina, the eye glasses in the brain organoids contained precursor cells of the lens and cornea tissues and demonstrated the connection of retinal neurons with brain regions. In the mammalian brain, nerve fibers coming from retinal ganglion cells connect with brain neurons – never before has this interaction been reproduced in vitro.

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A significant limitation of the study is that the viability of organoids drops sharply after the 60th day, they cannot generate mature cells of eye tissues. In future studies, the group plans to develop strategies to preserve the viability of eye glasses for a long period of time in order to use them to study the mechanisms that cause retinal disorders.

Article by E.Gabriel et al. Human brain organoids assemble functionally integrated bilateral optic vesicles is published in the journal Cell Stem Cell.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on Eurekalert materials: Brain organoids develop optical cups that respond to light.


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