Neurodegenerative Biomarkers

Abstract:

Primary open angle glaucoma (POAG) is a neurodegenerative disease of the visual pathway in which irreversible blindness result from progressive loss of retinal ganglion cells (RGCs). Intraocular pressure or visual field testing are unreliable methods to screen for POAG. As such, there is currently no effective clinical method for diagnosing POAG at an early stage. Our goal is to identify and develop POAG biomarkers which can be utilized for early diagnosis. We hypothesize that the degeneration of RGCs result in leakage of specific neuronal proteins into the blood, and that autoantibodies developed against these neuronal proteins can be utilized as a POAG biomarkers. These autoantibodies will be present in the serum or tear film in small quantity. Therefore, the goal of this proposal is to develop sensitive proteomic assays to these autoantibodies, and test them in POAG patients. Previous studies by other investigators have examined autoantibodies to inflammatory markers. However, to our knowledge, little is known about autoantibodies to neuronal proteins emanating from dying neurons. In preliminary work, we have already developed an assay to detect low levels of autoantibodies against these neuron-specific proteins, such as tau, MAP, and neuron enolase. Furthermore, our preliminary data have demonstrated elevated autoantibody levels of specific neuronal proteins in POAG patients recruited at the Duke Eye Center. Here, we propose to expand our preliminary work into a larger clinical study and validate these autoantibodies as serum and tear film biomarkers.