Innovative ‘Human Optic Nerve-on-a-Chip’ platform development

Description

This project proposes the development of an innovative ‘Human Optic Nerve-on-a-Chip’ platform, a multi-organ microfluidic device designed to meet the urgent need for physiologically relevant models for glaucoma research. Glaucoma is one of the leading causes of blindness in adults and is characterised by the progressive degeneration of retinal ganglion cells (RGCs), which collect visual information captured and processed by the retina and transmit it to the brain via their axons, which form the optic nerve. This cell loss is due to a combination of mechanical, inflammatory and genetic factors.

This platform will reproduce the biology of the human optic nerve head – the exit structure of ganglion cell axons and particularly vulnerable in AMD – by unidirectionally connecting retinal organoids to brain assembloids via a three-dimensional channel allowing the growth and fasciculation of RGC axons. This device, which enables the reconstruction of a 3D optic nerve, represents a major advance over current 2D models.

In order to accurately reproduce the pathogenic environment of glaucoma, ON-Chip will incorporate an inflammatory component by including glial cells and microglia, resident cells of the nervous system responsible for monitoring retinal homeostasis, as well as inflammatory monocytes that are specifically observed in retinal degeneration. ON-Chip will offer the possibility of controlling the deformation of the three-dimensional channel to induce mechanical stress on the neuronal extensions of RGCs in order to mimic the mechanical stress induced by the abnormal elevation of intraocular pressure characteristic of GPAO. Finally, retinal organoids can be genetically modified to introduce genetic variants observed in certain glaucoma patients.

Through the use of genetically encoded sensors to monitor retinal ganglion cell homeostasis in real time, the platform will enable dynamic assessment of optic nerve functionality. By combining relevant pathological conditions such as neuroinflammation or elevated intraocular pressure with patient-specific genetic risk factors, ON-Chip will provide a personalised and unparalleled model of glaucoma pathophysiology. This system will be particularly suitable for pharmacological screening, gene therapy validation and regenerative medicine applications.