Year: 2021
Type: article
Abstract: Zika virus (ZIKV), a mosquito-borne flavivirus, can cause severe eye disease and even blindness in newborns. However, ZIKV-induced retinal lesions have not been studied in a comprehensive way, mechanisms of ZIKV-induced retinal abnormalities are unknown, and no therapeutic intervention is available to treat or minimize the degree of vision loss in patients. Here, we developed a novel mouse model of ZIKV infection to evaluate its impact on retinal structure. ZIKV (20 plaque-forming units) was inoculated into neonatal wild type C57BL/6J mice at postnatal day (P) 0 subcutaneously. Retinas of infected mice and age-matched controls were collected at various ages, and retinal structural alterations were analyzed. We found that ZIKV induced progressive neuronal and vascular damage and retinal inflammation starting from P8. ZIKV-infected retina exhibited dramatically decreased thickness with loss of neurons, initial neovascular tufts followed by vessel dilation and degeneration, increased microglia and leukocyte recruitment and activation, degeneration of astrocyte network and gliosis. The above changes may involve inflammation and endoplasmic reticulum stress-mediated cell apoptosis and necroptosis. Moreover, we evaluated the efficacy of preclinical drugs and the safety of ZIKV vaccine candidate in this mouse model. We found that ZIKV-induced retinal abnormalities could be blocked by a selective flavivirus inhibitor NITD008 and a live-attenuated ZIKV vaccine candidate could potentially induce retinal abnormalities. Overall, we established a novel mouse model and provide a direct causative link between ZIKV and retinal lesion in vivo, which warrants further investigation of the underlying mechanisms of ZIKV-induced retinopathy and the development of effective therapeutics.
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,170
Funders: Amon G. Carter Foundation, John S. Dunn Foundation, University of Texas System, Gillson Longenbaugh Foundation, Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation, Retina Research Foundation, Sealy and Smith Foundation, Texas Alzheimer's Research and Care Consortium, National Institutes of Health, National Eye Institute, National Institute of Allergy and Infectious Diseases, National Center for Advancing Translational Sciences
Awards: Mechanisms of Retinal Neuronal Injury, Regulation of Ebola virus replication by the host ubiquitin system, Pathogenic Role of EPAC1 Signaling in Retinopathy of Prematurity, Investigation of Zika virus-induced retinopathy using developing mouse retina, Mechanism of death of bystander retinal cells during MCMV infection, UTMB Clinical and Translational Science Award, Neuroprotective Role of Sirt6 in Glaucoma
OpenAlex ID: W3165181070