Reducing Inflammation to Protect Vision in Glaucoma

Glaucoma is characterized by retinal ganglion cell (RGC) degeneration. Inflammatory glial cells interact with RGC axons at the optic nerve head, the main site of injury. This project will use human stem cell-derived models and microfluidic devices to study how these inflammatory interactions contrib

Glaucoma is characterized by retinal ganglion cells (RGCs) degeneration. Inflammatory astrocytes and microglia closely associate with RGC axons at the optic nerve head, the primary site of injury. To investigate how this inflammatory crosstalk contributes to axonal degeneration in glaucoma, human stem cell-derived models and microfluidic devices will be employed to specifically study RGC axons.

The innovative aspects include: (1) the use of human pluripotent stem cell (hPSC)-derived models to overcome species differences that limit rodent studies; (2) the development of a novel microphysiological platform using microfluidics to mimic RGC compartmentalization and the spatial organization of inflammatory glial cells along proximal RGC axons in the optic nerve head; (3) the use of a combinatorial therapeutic strategy consisting of two potent NF-kB inhibitors to target inflammatory glia and prevent RGC degeneration; and (4) the establishment of a broadly translatable platform for studying astrocyte-microglia inflammatory crosstalk observed in neurodegenerative diseases.

This study will advance our understanding of how inflammatory interactions between astrocytes and microglia contribute to retinal ganglion cell (RGC) axonal degeneration in glaucoma. Using a human stem cell-based microphysiological model that recapitulates key features of the optic nerve head, we will identify mechanisms driving neuroinflammation and evaluate therapeutic strategies that target harmful glial responses. This human-based system will provide mechanistic insights into astrocyte-microglia interactions in glaucoma and will serve as a strong foundation for future translational studies focused on preventing RGC axonal loss.