Human induced pluripotent stem cells (iPSCs) have been used to generate brain organoids containing an optic cup, according to a study in Cell Stem Cell. The organoids spontaneously developed bilaterally symmetric optic cups from the front of the brain-like region, demonstrating the intrinsic self-patterning ability of iPSCs in a highly complex biological process.
“These organoids can help to study brain-eye interactions during embryo development, model congenital retinal disorders, and generate patient-specific retinal cell types for personalised drug testing and transplantation therapies,” commented senior study author Jay Gopalakrishnan of University Hospital Düsseldorf.
Previously, the production of optic cups from pluripotent stem cells focused on generating the pure retina. Additionally, optic cups and other 3D retinal structures had not been functionally integrated into brain organoids.
By modifying a protocol previously used to turn iPSCs into neural tissue, the team enabled human brain organoids to form optic cups, which appeared as early as 30 days and matured as visible structures within 50 days, a time frame paralleling that of retinal development in the human embryo.
Across 16 independent batches from four iPSC donors, they generated 314 brain organoids, 72% of which formed optic cups, showing reproducibility. The structures contained diverse retinal cell types, which formed electrically active neuronal networks responsive to light, with optic cups containing lens and corneal tissue, and exhibiting retinal connectivity to brain regions. “In the mammalian brain, nerve fibres 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,” Dr Gopalakrishnan said.
Jay Gopalakrishnan, et al. Human brain organoids assemble functionally integrated bilateral optic vesicles, Cell Stem Cell, 2021, ISSN 1934-5909, doi.org/10.1016/j.stem.2021.07.010.