Does Vision Loss Affect Tauopathy in the Brain

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Does Vision Loss Affect Tauopathy in the Brain SUMMARY Tau is a member of the microtubule-associated proteins family, which is mainly expressed by neurons, especially in their axons where it controls the polymerization and stabilization of the microtubules and regulates axonal transport. Tauopathies, characterized by abnormal intracellular accumulation of aggregated and/or hyperphosphorylated tau within neurons, is a hallmark of Alzheimer's disease (AD) and a number of other disorders including frontotemporal dementia with parkinsonism-17 (FTDP-17), Pick disease, progressive supranuclear palsy and corticobasal degeneration. Tauopathies are among the most crippling conditions that affect our rapidly growing aging population. Due to the lack of effective diagnostics, preventative means, and treatments, these diseases significantly impair the daily life of patients and markedly impose financial costs to them, their family members and society. The retina is an extension of the neural network of the brain. It shares many similar pathophysiological changes and underlying mechanisms with the brain during neurodegenerative diseases including AD. Growing consensus among researchers and clinicians is that the interdependency of eye and brain maybe more intricate than we thought. While dysfunction of the central nervous system (CNS) will influence visual function in different ways, emerging evidence suggests that visual impairment may contribute to neurodegeneration in the brain. Multiple cohort clinical studies demonstrate that visual-impairment diseases including glaucoma and cataract increase risk of developing dementia and AD, and cataract extraction is significantly associated with lower risk of dementia development. However, conflicting studies remain. Considering clinical studies cannot control for confounding variables such as age, the stage when cognitive impairment becomes noticeable, and the extent of visual impairment, it is not surprising that conflicting results were reported, and a cause-and-effect relationship from vision loss to AD could not be tested. Therefore, we propose to use well-controlled animal experiments to test the hypothesis that visual impairment accelerates tauopathy in the brain. We will test this hypothesis using two distinct visual impairment models that model retinal neuronal injury and visual deprivation as seen in glaucoma and cataract, respectively, but at much severer extents so that we can unambiguously test the relationship between vision loss and tauopathy. This proposal is highly in line with the objectives of “NOT-AG-21-044” to “investigating how functional changes in sensory systems impact the development and progression of AD”. Completion of the proposed studies will provide important new knowledge that will fill the current knowledge gaps and provide scientific base for preventing and treating tauopathy by restoring good vision. Models developed in this project will serve as the foundation for further investigation of mechanisms by which visual loss causes neurodegeneration in tauopathy.