IOP-Related Gene Responses in the Optic Nerve Head and Trabecular Meshwork

The goal of this project is to investigate how mild and repeat intraocular eye pressure elevations modify the molecular mechanisms in ocular tissues (trabecular meshwork and optic nerve head) implicated in glaucoma pathogenesis.

Elevated intraocular pressure (IOP) is a leading risk factor for primary open-angle glaucoma. Yet, the cellular events that comprise protective homeostatic IOP responses, or deleterious events leading to tissue injury, are currently poorly understood. We will investigate how mild and repeat IOP elevations modify the molecular mechanisms in ocular tissues implicated in glaucoma pathogenesis.

The principal innovations are: (1) the CEI model allows us to control the duration and IOP elevation level, as well as the timing between repeat exposures, which is not feasible with chronic glaucoma models. By delivering precise IOP doses, we will identify the earliest TM and ONH cellular responses. (2) We will quantify in vivo TM and ONH gene responses simultaneously in the two tissues involved in glaucoma pathology. This may uncover important pathways that are protective or injurious. (3) We will understand how cellular reactions to repeat IOP elevations can cumulatively lead to injury.

Elevated intraocular pressure (IOP) is a major risk factor for glaucoma. In this study, we will investigate which genes respond to mild and repeat IOP elevations in the trabecular meshwork and optic nerve head, the ocular tissues where glaucoma pathology accumulates. Our studies will lead to new approaches for treating elevated IOP and new mechanisms for protecting the ONH.