Understanding Alterations in an Early Experimental Glaucoma Model

Our goal is to identify the cellular and molecular alterations underlying optical coherence tomography early structural change in a non-human primate experimental glaucoma (EG) model.

In Aim 1, we will compare protein expression changes within 30-degree optical coherence tomography (OCT) optic nerve head (ONH) sectors demonstrating 30% nerve fiber thickness loss in glaucoma vs control eyes. In Aim 2, will colocalize immunohistochemistry section to a virtual OCT B-scan generated from high-resolution isotropic OCT ONH data set. We will compare the longitudinal OCT deep ONH structural and reflectance intensity changes from baseline to protein expression alterations at equivalent locations in the EG versus control eyes.

Our strategies to colocalize immunostained sections to nerve fiber layer loss detected by optical coherence tomography (OCT) and colocalize these sections to OCT structural and intensity change within a best-matched virtual OCT B-scan are innovative. Previous studies have looked at global measures by immunohistochemistry that do not account for the focal nature of glaucomatous damage. By colocalization, we aim to examine changes in sectors that have not yet shown significant OCT thinning, allowing us to investigate cellular alterations across a range of disease stages within the same eye.

The translational importance of this work will be two-fold. First, it will provide strong support and perhaps mechanistic direction for the treatment of early OCT-detected structural change in human eyes at risk for developing glaucoma such as those with suspicious optic discs or ocular hypertension. Second, it will advance our understanding of early glaucoma pathophysiologic mechanisms and in so doing foster ONH-targeted neuroprotective interventions designed to stabilize or reverse the neuropathy of glaucoma early in its course.