Researchers in the Department of Ophthalmology, Visual and Anatomical Sciences at Wayne State University School of Medicine discovered for the first time that Zika virus can cause glaucoma in experimental models.
Pawan Kumar Singh, Ph.D., a research scientist in the laboratory of Associate Professor Ashok Kumar, Ph.D., is the lead author of the study, published this week in the journal mSphere, a peer-reviewed journal of the American Society of Microbiology.
Zika virus, or ZIKV, has emerged as a public health threat and poses significant challenges in reproductive health worldwide. While congenital ZIKV infection has been shown to cause neurological disorders, primarily microcephaly – abnormal shrinking of the head circumference – several clinical studies have linked ZIKV to ocular deformities in infants. These include retinal lesions, microphthalmia, hemorrhagic retinopathy, retinal pigmented epithelium mottling, optic neuritis and hypoplasia of the optic nerve.
“The eye is protected from systemic infection due the presence of a protective barrier called the blood retinal barrier. Previous studies from our laboratory have shown that ZIKV has the ability to infect and replicate in cells making the blood retinal barrier, hence potentially allowing the entry of ZIKV into the eye,” Dr. Kumar said. “As the research interest of our laboratory is to study host-pathogen interactions, Dr. Singh made an unexpected observation that ZIKV-infected mice had an increased intraocular pressure, or IOP, in their eyes. Since elevated IOP is one of the hallmarks of glaucoma, the second most common blinding eye disease, we pursued this new line of investigation.”
Associate Professor Anju Goyal, M.D., and Professor and Chair Mark Juzych, M.D., were also study team members.
“Glaucoma is classically viewed as a genetic and age-related disease and has rarely been associated with congenital infection among infants. One of the unique aspects of this study is the link between infectious agents as triggers of glaucoma. Because of the complexity of glaucoma pathobiology, our study may provide other avenues to study this disease,” Dr. Juzych said.
Recent clinical cases from ZIKV-affected countries have raised global alarm that there is a possible link between congenital glaucoma and ZIKV infection.
“These clinical reports and our observation of increased IOP in an experimental ZIKV infection model triggered our interest to confirm the potential link and determine underlying mechanisms,” Dr. Singh said. “In this study, we showed that ZIKV can readily infect human trabecular meshwork cells, a key cell type that regulates the flow of aqueous humor and maintains normal IOP in our eyes. Moreover, ZIKV was able to replicate and produce infectious virions in these cells and caused inflammation. Most importantly, eyes of ZIKV-infected mice exhibited glaucomatous pathology characterized by death and loss of retinal ganglion cells, and damage to the optic nerve resulting in disruption of axonal transport.”
Despite the findings, several questions remain. The scientists are now investigating the detailed underlying mechanisms for ZIKV-induced glaucoma to identify potential targets for therapeutic intervention.
In another recent study published in the journal The Ocular Surface, Dr. Singh showed that ZIKV can infect human primary corneal epithelial cells.
“ZIKV has been shown to be present in the tears of human and experimental mouse models, leading us to conclude the potential risk of ZIKV transmission during corneal transplants, especially those residing in endemic zones of ZIKV infections,” Dr. Kumar said.
As most of the previous studies have focused on ZIKV-induced ocular abnormalities in the posterior segment of the eye, specifically in the retina, “to our knowledge, these two studies are the first to show its involvement in the anterior segment of the eye,” he said.