An international research team has developed a new method to improve the function and longevity of retinal organoids, three-dimensional tissue cultures derived from human stem cells. The team, led by Professor Volker Busskamp at University Hospital Bonn, the University of Bonn, and the Institute of Molecular and Clinical Ophthalmology Basel, addressed a longstanding challenge in maintaining retinal ganglion cells deep within organoids for extended periods.
In densely packed tissues such as retinal organoids, limited access to nutrients and oxygen often leads to cell death. To solve this problem, researchers combined human stem cell-derived retinal organoids with endothelial cells. These vascular cells integrated into the organoids and formed lumen-like networks capable of transporting nutrients and oxygen—key factors in preserving sensitive retinal ganglion cells. In living organisms, these ganglion cell axons form the optic nerve that transmits visual information from the retina to the brain.
The team tested various methods for introducing vascular cells and found that pre-cultured endothelial cells integrated most effectively when added to already-formed organoid spheres. This technique preserved natural developmental processes while significantly increasing the survival rate of ganglion cells. Further analysis revealed that cell types within these vascularized retinal organoids (vROs) differentiated normally; optic nerve cells not only survived longer but also achieved greater functional maturity.
To assess ganglion cell activity, scientists used microelectrodes and microfluidic devices that supported stable axon growth. In vROs, retinal ganglion cells exhibited increased electrical activity—they sent signals more frequently, synchronously, and with higher intensity compared to non-vascularized counterparts. When stimulated with light using optogenetic techniques, these cells produced stronger and more reliable responses. After several weeks of maturation, vROs developed functional light-signal pathways: photoreceptors responded to light stimuli and correctly transmitted signals to ganglion cells with typical ON, OFF, and ON-OFF response patterns.
Professor Busskamp is also a member of the Transdisciplinary Research Area "Life and Health" at the University of Bonn.
Additionally, the vascularized organoids responded dynamically under low-oxygen conditions (hypoxia). The artificial vessels formed new networks similar to those seen in certain retinal diseases. This capability enables researchers to model conditions like retinopathy of prematurity in vitro and test potential therapies.
According to the research team, their approach is straightforward to implement and can be adapted for other types of organoid models. Vascularized retinal organoids now offer advanced human retinal models containing functional ganglion cells capable of developing light-signal pathways in laboratory settings. These improvements create new opportunities for studying eye diseases, evaluating drugs, and exploring future treatments.
