Advancing Retinal Research with Vascularized Retinal Organoids

Retinal organoids (ROs) have revolutionized the study of retinal development and disease by closely mimicking the architecture and function of the human retina. These lab-grown models provide an unprecedented platform for studying vision-related disorders, testing new treatments, and uncovering the intricacies of retinal biology. However, traditional ROs face a critical limitation: the lack of a functional vasculature. Without a vasculature, the supply of nutrients and oxygen is inadequate, leading to cell death and impaired survival of retinal ganglion cells (RGCs). To address this issue, we have developed an innovative vasculature-like system within ROs by incorporating iPSC-derived endothelial cells into the organoid structure. This advance significantly improves nutrient and oxygen delivery, thereby enhancing RGC survival and function.

Another major challenge in retinal research has been the inability of RGCs within ROs to extend axons as they do in vivo. This limitation limits their effectiveness in modeling retinal function and circuitry, as well as neurodegenerative diseases. Here, we combined the vascularized ROs with a microfluidic system to provide stable axonal projections. RGC axons are guided over electrodes on multielectrode arrays (MEAs), allowing direct recording of RGC activity and assessment of RGC functional properties in real time. The result is a more physiologically relevant model that overcomes key limitations of traditional retinal organoids. These vascularized ROs represent a major advance in vision research. By improving RGC viability and function, they enhance the utility of ROs for studying retinal diseases, investigating neuroprotective strategies, and developing novel therapeutic approaches. This innovation paves the way for deeper insights into retinal diseases and provides a transformative platform for future biomedical breakthroughs. This work is funded by DFG.