Administrative Supplement: Investigation of Zika Virus-Induced Retinopathy using Developing Mouse Retina

ABSTRACT More than 60% of people with Alzheimer’s disease (AD) exhibit decline in visual function(s) that significantly affects life quality of AD patients. Meanwhile, poor vision also contributes to cognitive decline. Nevertheless, few studies have been done to address the needs of how to prevent or treat vision loss in AD patients. One of the major focuses in this award is to characterize retinal morphological, pathological and functional changes after Zika virus (ZIKV) infection, and understand potential mechanisms (e.g. apoptosis and inflammation) by which ZIKV-induced retinal neurodegeneration. In this application for Administrative Supplements, we propose to conduct experiments to generate preliminary data to determine if ZIKV induces tau hyperphosphorylation and aggregation, a hallmark and key mediator of AD, and test if tauopathy, similar to what happens in AD, is a key player in retinal neurodegeneration during ZIKV infection and if ZIKV infection accelerates AD pathology in the retina. The feasibility of the work proposed is strongly supported by data generated from the research progress of the parental award and by our preliminary data. Based on pilot data from this work, in the future, we will apply for funding to further determine cellular and molecular mechanisms by which ZIKV induces tau hyperphosphorylation and aggregation, tau-mediated retinal neurodegeneration, and accelerated AD pathology. The proposed pilot work, together with future studies following this work, is expected to significantly advance the mechanistic understanding of the potential role of RNA viruses in the injury of retina and brain in AD, which may facilitate the development of novel strategies to protect neurons in AD