Project title: Study Zika virus-induced retinopathy using developing mouse retina SUMMARY The recent outbreak of Zika virus (ZIKV) in the Americas has caused significant public health concern. ZIKV infection has been linked to neurological autoimmune disorder Guillain-Barr Syndrome in adults and microcephaly in fetuses and infants born to mothers infected with ZIKV during pregnancy. In addition to neuronal damage in the brain, infants with ZIKV congenital infection are associated with high rate of ocular abnormalities in which the most common lesions are retinal lesions, chorioretinal atrophy and optic nerve abnormalities. However, mechanisms of ZIKV-induced retinal abnormalities are completely unknown and no therapeutic intervention is available to treat or minimize the degree of vision loss in the patients. Mouse retinal development during the first 3 weeks after birth is very similar to the process of third-trimester human retinal development; and ex vivo retinal explant from neonatal mice develops very similarly to the retina in vivo and generates all different retinal cell types in the appropriate layers. Taking these advantages, we will test the hypothesis that the developing retina is a platform to study ZIKV-induced retinal abnormalities and test compounds for the treatment of disease. This application will, for the first time, use postnatally developing mouse retina as a platform to develop and characterize ZIKV-induced retinopathy in vivo and ex vivo. It will compare the difference of three ZIKV strains and evaluate the efficacy of antiviral, anti-inflammatory or anti- apoptotic agents. The research is expected to significantly advance the understanding of ZIKV-induced retinopathy and facilitate the development of novel therapeutic strategies. This proposal directly addresses the following areas of high priority to study ?Zika Virus (ZIKV) Complications?: 1) understand the mechanisms by which ZIKV affects the developing nervous system and other organ systems; 2) characterize the association of ZIKV infection with ocular phenotypes; 3) identify effective treatments for exposed infants with and without microcephaly as they develop into childhood.
Mouse retinal development during the first 3 weeks after birth is very similar to the process of third-trimester human retinal development. This project is to use postnatally developing mouse retina as a platform to study ZIKV-induced retinopathy and investigate the therapeutic effects of compounds that exhibit potential activities to alleviate congenital Zika syndrome.
