ON-CHIP
Glaucoma, and in particular primary open-angle glaucoma (POAG), is a multifactorial neurodegenerative disease driven by complex interactions between intraocular pressure, genetic, and systemic factors. It leads to irreversible retinal ganglion cell (RGC) progressive degeneration and optic nerve degeneration, with limited therapeutic options currently available. Among emerging approaches, stem cell therapies offer real hope for patients; however, their efficacy remains limited by poor graft survival and integration, and the integration in a damaged optic nerve environment remains a challenge.
Coordinator
Research director
Inserm
Institutions and establishments involved
Work Packages
Sorbonne Université; Institut du Cerveau; Institut de la Vision;
The project is structured around three interconnected objectives:
- WP1: Design and fabricate the optic nerve-on-a-chip device, incorporating unidirectional
connected retinal to brain organoids and key cellular components involved in ONH
homeostasis. - WP2: Model glaucoma by exposing the system to POAG-relevant stressors, analyzing their
effects on RGC function and survival. - WP3: Assess therapeutic strategies, including iPSC-derived cell transplantation, gene
therapy, and neuroimmunomodulation to improve graft integration
Research program
This project proposes the development of a “Human Optic Nerve-on-a-Chip” platform—an innovative, multi-organ microfluidic device designed to address the urgent need for physiologically relevant systems in glaucoma research. The platform will mimic human optic nerve head, a structure critically stresses during POAG, biology by unidirectionally connecting retinal organoids to brain assembloids, enabling inter-organ neural circuit integration through a sizeable 3D channel representing an unprecedented advancement over current static or 2D models.
Pushing the boundaries of neural modeling, the ON-Chip system will, for the first time, incorporate cells from the monocyte-phagocyte lineage, introducing microglial components into a complex glia-neuron interface. Leveraging genetically encoded biosensors for real-time monitoring of RGC homeostasis, the platform will enable dynamic assessment of optic nerve functionality. By integrating disease-relevant conditions such neuroinflammation and elevated intraocular pressure and patient-specific genetic risk factors, ON-Chip will offer a powerful, personalized model of glaucoma pathophysiology. This system will be ideally suited for drug screening, gene therapy validation, and regenerative medicine applications.
Résultats attendus
In summary, the ON-Chip platform represents a transformative step in glaucoma research, combining technological innovation with biological relevance to deepen our understanding of disease mechanisms and accelerate the development of targeted therapies.
Le consortium
This ambitious project brings together three leading French neuroscience institutes—Institut de la Vision, NeuroSpin (NeuroSU), and the Institut du Cerveau (ICM)—each contributing complementary expertise in microfluidics, organoid biology, and neurodegeneration. Their geographic proximity and established collaborations will ensure fluid communication and effective coordination throughout the project.
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