In recent medical advances, a significant study reported in the renowned journal, iScience, offers invaluable knowledge on the impact of Zika virus infection during pregnancy, specifically on the eye, and opens up potential routes for therapeutic treatments. The research has been conducted by an expert team from the Department of Ophthalmology, Visual and Anatomical Sciences at the Wayne State University School of Medicine.
The study, titled “Targeting ABCG1 and SREBP-2 mediated cholesterol homeostasis ameliorates Zika virus-induced ocular pathology,” sheds light on the role of cholesterol metabolism in the emergence of eye abnormalities related to the Zika virus (ZIKV). This virus has been recognized as a global health risk, posing significant threats to reproductive health.
Congenital exposure to ZIKV has previously been linked to neurological disorders predominantly microcephaly, a condition characterized by an abnormally small head circumference. However, ZIKV has also been connected to eye abnormalities in newborns, such as retinal lesions, microphthalmia, hemorrhagic retinopathy, optic neuritis, hypoplasia of the optic nerve, and mottling of the retinal pigmented epithelium.
Despite the severe neurological and ocular abnormalities caused by ZIKV infection in infants, there currently are no specific vaccines or antiviral treatments available. The research team, led by Professor Ashok Kumar, sought to understand the molecular mechanisms behind ZIKV-related eye abnormalities, focusing on cellular metabolism. This understanding could help identify potential targets for therapeutic intervention.
The research centered on two key regulators of cholesterol metabolism, ATP-binding cassette transporter G1 (ABCG1) and sterol response element binding protein 2 (SREBP-2). Their experiments demonstrated that increased ABCG1 activity, coupled with the inhibition of SREBP-2, reduced ZIKV replication by lowering cholesterol levels.
The team’s in vivo studies on mouse models, which had ZIKV-induced chorioretinal lesions, showed that treatment with an LXR agonist or SREBP-2 inhibitor lessened ocular abnormalities associated with ZIKV infection. This improvement was accompanied by a decrease in inflammatory mediators and an increase in antiviral response genes.
Postdoctoral fellow Sneha Singh, Ph.D., emphasized the complex relationship between cholesterol metabolism and ZIKV infection in the eye. She suggested that targeting cholesterol pathway components, such as ABCG1 and SREBP-2, could provide effective therapeutic strategies for mitigating ZIKV-induced ocular complications.
Professor Kumar also stressed that the findings from this study could potentially apply to other enveloped viruses such as West Nile virus, Japanese encephalitis virus, and Dengue virus. His team is currently using a lipidomics approach to identify lipid molecules with both proviral and antiviral properties. Their ultimate goal is to discover new antiviral therapeutics.
This research showcases Wayne State’s commitment to advancing scientific knowledge and addressing global health challenges. The university’s dedication to excellence in scientific inquiry is evident in this interdisciplinary collaboration and innovative methodologies. As Dr. Ezemenari M. Obasi, vice president for research at Wayne State, commended, Dr. Kumar’s research team is leading the way in developing groundbreaking solutions for eye abnormalities caused by the Zika virus.
The study was carried out with support from the National Institutes of Health’s National Eye Institute.
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