COMMENTARY

Blood, Sweat, and Tears? The Presence of Zika in the Eye

Brianne N. Hobbs, OD

Disclosures

March 21, 2017

Zika Virus Infection in Mice Causes Panuveitis With Shedding of Virus in Tears

Miner JJ, Sene A, Richner JM, et al
Cell Rep. 2016;16:3208-3218

With its recent downgrading by the World Health Organization from acute outbreak to a chronic problem, Zika has faded somewhat from the spotlight. Yet every day, we discover more about this virus. The frantic race to deepen our understanding of Zika is necessary, given that so much is still unknown about its transmission and effects on the body. Although there are tests for the Zika virus, there is currently no vaccine and no treatment.

Zika has disastrous effects on the developing central nervous system, so it is no surprise that one of its targets is the eye. In congenital Zika, ocular effects include chorioretinal atrophy, optic nerve changes, colobomas, retinopathy, and—most recently discovered—glaucoma.[1] Less is known about the effects of Zika on the adult eye, but conjunctivitis is the most common ocular manifestation, followed by uveitis. Zika tends to persist in the eye long after it has been cleared from the serum, probably owing to the protection from the immune system that the eye offers as an immunoprivileged site.

It is critical to understand where in the eye the Zika virus resides; its effect when there; and its possible transmission through ocular fluids, such as tears.

Study Summary

A group of researchers explored the effects and persistence of Zika in the eye in a mouse model. The Zika virus does not replicate efficiently in adult mice, so specific interferon signaling pathways had to be interrupted in the mice to allow the virus to replicate as it does in humans. Miner and colleagues inoculated adult mice with the Zika virus, and then studied the pathology induced by the virus in various organ systems, including the eye.

In mice, Zika RNA was detected in ocular tissues both initially and 28 days after inoculation. Of particular importance, Zika RNA was detected in the tears and lacrimal glands of the infected mice 7 days after inoculation. Researchers also found that the Zika virus persisted in the eyes, brain, and spleen even after the virus had been cleared from the serum.

In adult infected mice, Zika RNA was found nearly ubiquitously throughout the eye, including in the cornea, iris, lens, retina, choroid, and optic nerve. The retinal pigment epithelium was particularly susceptible to viral invasion, with viral RNA levels approximately 100 times higher there than in the optic nerve. In young mice infected with Zika early in the postnatal period, apoptosis was detected in multiple components of the visual pathway, including the optic tract, lateral geniculate nucleus, and visual cortex.

Viewpoint

The finding from this study that received the most media fanfare, and rightfully so, was the presence of Zika genetic material in tears. If infectious Zika particles can persist in tears at a high enough level to cause relatively easier viral transmission, then this is an important public health concern.

There is currently at least one case of Zika infection in which the mode of transmission is unknown. It is possible that ocular fluids, such as tears, played a role in this case, because the patient had unusually high levels of virus throughout his body. Of note, tears were not confirmed as a mode of transmission in this study; the Zika RNA observed in the tears was determined to be noninfectious and incapable of transmitting the disease. Additional studies are needed to further investigate whether infectious viral particles are present in the tears, or if the tears contain only noninfectious Zika RNA.

Another important finding of the study was the persistence of Zika virus in the ocular tissues, especially the retina. Other viruses, such as Ebola virus,[2] have been found to persist in the eye long after they are cleared from the serum, and this is probably the case with Zika as well. This could change standard practice protocols in corneal transplants, given that corneas from Zika-infected patients would have to tested and potentially discarded.

The preferential accumulation of Zika in the retinal pigment epithelium and choroid is interesting, because it might potentially explain the chorioretinal atrophy and maculopathy common in congenital Zika infections.

The major limitation of this study is simply that it was conducted in mice and not in humans; thus, the results are not directly applicable to humans.

In conclusion, this study brings to light the potential for tears to transmit the Zika virus, a possibility that should certainly be investigated further.

Abstract

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