Optic Nerve-on-Chip: A 3D iPSC-Based Platform for Vision Repair and Drug Discovery

Description

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.

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 diseaserelevant 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.