The ability to derive mammalian retinas from stem cells has transformed the study of vision biology, leading to the creation of retinal organoids. These organoids mimic several structural and molecular features of the human retina but remain functionally immature, lacking the complex synaptic connectivity, light discrimination, and electrical signaling characteristic of in vivo tissue. This limitation has become a major bottleneck for using organoids in disease modeling, drug discovery, and vision restoration research.
To fully harness the potential of retinal organoids, it is essential to understand how electrical activity drives functional maturation in the developing retina and to recreate those cues in vitro. In vivo, spontaneous and light-driven electrical events shape neuronal connectivity and circuit specialization during development. However, these processes remain poorly characterized and have not yet been translated into organoid systems.
Overall objectives:
The project NeuFRO (NeuroFunctional Retinal Organoids) aims to overcome the functional limitations of current organoid models by decoding and reproducing the electrophysiological cues that guide retinal development. Specifically, we will:
1) Map the spatiotemporal patterns of electrical activity in developing mouse retina, using advanced electrophysiology combined with milli- to nanometer–scale imaging.
2) Decode the space-time electrical code that governs neuronal self-organization and circuit formation, employing computational models based on Hodgkin–Huxley and linear–nonlinear frameworks.
3)Apply bioinspired electrical stimulation to immature mouse and human retinal organoids using an innovative “sandwich” electrophysiology approach to induce naturalistic network activity.
Expected impact
NeuFRO will establish a new paradigm for functional organogenesis in vitro, generating retinal organoids that exhibit authentic neuronal connectivity and physiological light processing. This interdisciplinary approach—combining developmental neurobiology, electrophysiology, and computational modeling—will enable the creation of bioelectronic human retinal models for mechanistic studies, therapeutic testing, and regenerative applications.
Beyond vision science, this project will provide a blueprint for engineering functional neural tissues, offering wide translational potential for neuroscience, bioengineering, and neuroprosthetics. By reducing reliance on animal models and improving predictive accuracy, NeuFRO contributes to ethical, sustainable, and personalized biomedical innovation.
