Glaucoma Neuroimaging in Humans and Experimental Animal Models

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Abstract The Aim of the parent project is to develop and apply an in vivo imaging model system to find out the structural-metabolic-functional brain relationships and eye-brain-behavior relationships in both humans and animal models of glaucoma for clinical and translational applications. Building on the opportunities provided by this unique technological platform, the goal of the supplementary project is to adapt these novel neuroimaging tools towards closing knowledge gaps on how scutellarin, a flavonoid that exhibits a number of neuroprotective effects on the brain and the eye, can preserve structure and function of the visual system in experimental glaucoma induced by chronic intraocular pressure (IOP) elevation. The results of this supplementary project may help determine if scutellarin can be a possible candidate as a novel neurotherapeutic agent for glaucoma treatment. Glaucoma is the leading cause of irreversible blindness worldwide with increasing prevalence due to the aging population. While IOP is clinically the only modifiable risk factor, glaucoma may continue to progress in some patients even after lowering IOP to normal levels, which indicates that additional key factors may be contributing to the glaucomatous pathogenesis. The primary objective of our research is to use the in vivo imaging model systems developed in the parent proposal to find out the structural-metabolic-functional brain relationships and eye-brain-behavior relationships in glaucoma. Results will be valuable for identifying glaucoma mechanisms not only within the eye but also the brain’s visual system, and how they interact and progress over disease severity to reflect behavioral performance. Specifically, using scutellarin, which is one of the major constituents of the herb Erigeron breviscapus, our supplementary project will propose that neuroprotective or neuroenhancing approaches to the visual system via oral scutellarin treatment may help guide more effective strategies for visual preservation and restoration beyond IOP lowering alone, which can in turn reduce the burden of this irreversible but preventable disease. The milestones of this supplementary project include the successful detection of (1) the amelioration of structural, metabolic or functional brain changes as measured by magnetic resonance imaging; and (2) the preservation of retinal structure and visual behavioral function measured by optical coherence tomography and optokinetics, upon oral scutellarin treatment in our experimental glaucoma model when compared to the sham treatment within the experimental period, along with histological confirmations. This project is built upon the glaucoma imaging expertise of Kevin C. Chan, PhD (PI), as well as the clinical and translational glaucoma insights by Joel S. Schuman, MD (Co-I). The team has been collaborating on glaucoma neuroimaging and neurotherapeutics over the past 10 years.