PROJECT SUMMARY Glaucoma is a leading cause of vision morbidity and blindness with irreversible damage to retinal ganglion cells. Identifying biomarkers for early detection of glaucoma are paramount for timely initiation of treatment for preservation of functional vision throughout life. This project uses a chronic ocular hypertension animal model that provides unique insight into the changes the eye undergoes as it transitions from health to fully-manifest glaucoma. Using advanced ocular imaging technologies and state-of-the-art image processing methods we will monitor longitudinal structural and functional ocular changes, both global and local, of each animal as they develop glaucoma. We will determine the response of the optic nerve to two of the major causes of glaucoma – intraocular pressure (IOP) and intracranial pressure (ICP) – by acutely modulating these pressures and quantifying changes in optic nerve deformation at different time points along the course of the follow-up. This will allow determining the role of these pressures at the various stages of glaucoma development and changes in the optic nerve resulting from chronic exposure to elevated IOP, also known as remodeling. Lastly, we will identify structural and functional features and locations in the eye that are associated with future development of glaucomatous damage. The outcome of this project will provide insight into sensitive ocular biomarkers and their timeline of occurrence for early detection of glaucoma. Our model and tools ensure that the results can be translated to humans with substantial impact on clinical care.