Spatial Responses to Elevated Pressure in the Human Optic Nerve Head

This project will use advanced spatial profiling to study the neuroinflammatory signature present in the optic nerve head of glaucomatous eyes

Glaucoma irreversibly damages retinal and optic nerve tissue, often in association with high eye pressure. Yet, how pressure affects this tissue in human eyes is unclear. Using a new human tissue model we profiled acute neuroinflammatory responses to pressure. We will compare these data to long-term changes present in glaucoma samples to uncover critical links between pressure and disease.

This project presents a unique synthesis of organ culture and cutting edge spatial molecular profiling. Together these techniques provide unprecedented power to profile the neuroinflammatory signaling induced by elevated intraocular pressure in the architecturally intact human optic nerve head, and provide key insights into early glaucoma pathogenesis.

Vision loss in all forms of glaucoma stems from progressive degeneration thought to be initiated by damage at the optic nerve head. Yet, most research on this tissue has been limited to animal or cellular models that lack several key architectural features of the human eye. Our proposal will use innovative approaches to directly profile key cellular and molecular responses linking elevated intraocular pressure to glaucoma in patient eyes, and share these findings with the public. Our goal is to identify key early responses in the human optic nerve head that, in time, contribute to adaptive or damaging degenerative cascades.