Zika and the Eye: Pieces of a Puzzle

Dias, João Rafael de Oliveira; Ventura, Camila V.; Freitas, Bruno de Paula; Guerra, Ricardo Luz Leitão; Ventura, Liana O.; Bravo-Filho, Vasco; Alemán, Tomás S.; Ko, Albert I.; Zin, Andréa; Belfort, Rubens; Maia, Maurício

doi:10.1016/j.preteyeres.2018.04.004

Cited by 34 publications

(26 citation statements)

References 168 publications

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“…The virus could reach the fetal circulation from the placenta and infect the RPE, retinal endothelial cells, and the retina [ 94 ]. The other possible pathway would be through axonal transport into the eye along the optic nerve [ 95 , 96 ], leading to ganglion cell layer (GCL) loss, foveal maldevelopment, and central chorioretinal abnormalities [ 97 ]. How ZIKV and other flaviviruses enter the eye in vivo remains to be determined.…”

Section: Experimental Models Of Ocular Zikv Complicationsmentioning

confidence: 99%

Ocular Manifestations of Emerging Flaviviruses and the Blood-Retinal Barrier

Singh

Kumar

2018

Viruses

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Despite flaviviruses remaining the leading cause of systemic human infections worldwide, ocular manifestations of these mosquito-transmitted viruses are considered relatively uncommon in part due to under-reporting. However, recent outbreaks of Zika virus (ZIKV) implicated in causing multiple ocular abnormalities, such as conjunctivitis, retinal hemorrhages, chorioretinal atrophy, posterior uveitis, optic neuritis, and maculopathies, has rejuvenated a significant interest in understanding the pathogenesis of flaviviruses, including ZIKV, in the eye. In this review, first, we summarize the current knowledge of the major flaviviruses (Dengue, West Nile, Yellow Fever, and Japanese Encephalitis) reported to cause ocular manifestations in humans with emphasis on recent ZIKV outbreaks. Second, being an immune privilege organ, the eye is protected from systemic infections by the presence of blood-retinal barriers (BRB). Hence, we discuss how flaviviruses modulate retinal innate response and breach the protective BRB to cause ocular or retinal pathology. Finally, we describe recently identified infection signatures of ZIKV and discuss whether these system biology-predicted genes or signaling pathways (e.g., cellular metabolism) could contribute to the pathogenesis of ocular manifestations and assist in the development of ocular antiviral therapies against ZIKV and other flaviviruses.

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Section: Experimental Models Of Ocular Zikv Complicationsmentioning

confidence: 99%

Ocular Manifestations of Emerging Flaviviruses and the Blood-Retinal Barrier

Singh

Kumar

2018

Viruses

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“…In another study, 15 patients who had macular abnormalities were also described, but these have not been reported in other outbreaks of Zika virus worldwide 2 . Changes in the optic nerve were also observed, such as hypoplasia, paleness and an increased excavation of the optical disk 2,5,18,19 .…”

Section: Discussionmentioning

confidence: 99%

Correlation between cephalic circumference at birth and ocular alterations in patients with microcephaly potentially associated with Zika Virus infection

Trigueiro

Neves²,

Aguiar³

et al. 2019

Rev. Assoc. Med. Bras.

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SUMMARY INTRODUCTION: The Zika virus (ZIKV) is an arbovirus isolated for the first time in 1947 and transmitted to humans by the Aedes aegypti mosquito. In Brasil, it was first detected in May 2015. Since then, ZIKV has been identified as the etiological agent of acute exanthematous disease in Brasil, and Neuropediatricians of the Recife warned about an epidemic of microcephaly, and the Brazilian Ministry of Health confirmed the association between ZIKV and Congenital malformations and neurological syndromes. The eye, as an extension of the developing brain, has been examined in patients with microcephaly and maternal history of ZIKV infection. METHODS: Twenty newborn patients with microcephaly, whose mothers had presumed Zika virus during pregnancy, were analyzed through medical records. The nonparametric chi-square statistic was used to verify the association between head circumference and ocular alteration at a significance level of 0.0001. RESULTS: The significance of P = 0.000 in the value of non-parametric chi-square statistics was lower than the value of α = 0.0001, demonstrating that, at a level of 0.0001, there is an association between head circumference and ocular alteration. CONCLUSION: Although the knowledge of the natural evolution of the disease is still scarce, the current evidence is strong enough to establish a causal relationship between ZIKV infection during pregnancy and the increased incidence of the microcephaly and serious eye alterations that lead to the severe lower vision of these children.

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“…ZIKV infection has been linked to an increase in severe neurological complications in newborns including microcephaly (Martines et al, ; Martines et al, ; Melo, Chimelli, & Tanuri, ), cerebral calcifications and retinal damage. Neurological disorders associated with ZIKV disease now include the Guillain‐Barré syndrome (GBS; (Piontkivska, Plonski, Miyamoto, & Wayne, ; Soto‐Hernandez et al, ; Styczynski et al, ; Wright et al, ), myelitis, meningoencephalitis (Medina & Medina‐Montoya, ), ophthalmic manifestations (de Oliveira Dias et al, ), and acute transient polyneuritis (Nascimento et al, ). GBS is a type of peripheral neuropathy condition involving nerves extending into the head, trunk and limbs in children and adults (Cao‐Lormeau et al, ; Parra et al, ).…”

Section: Infectious Agentsmentioning

confidence: 99%

The role of teratogens in neural crest development

Cerrizuela

Vega-Lopez

Aybar

2020

Birth Defects Research

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The neural crest (NC), discovered by Wilhelm His 150 years ago, gives rise to a multipotent migratory embryonic cell population that generates a remarkably diverse and important array of cell types during the development of the vertebrate embryo. These cells originate in the neural plate border (NPB), which is the ectoderm between the neural plate and the epidermis. They give rise to the neurons and glia of the peripheral nervous system, melanocytes, chondrocytes, smooth muscle cells, odontoblasts and neuroendocrine cells, among others. Neurocristopathies are a class of congenital diseases resulting from the abnormal induction, specification, migration, differentiation or death of NC cells (NCCs) during embryonic development and have an important medical and societal impact. In general, congenital defects affect an appreciable percentage of newborns worldwide. Some of these defects are caused by teratogens, which are agents that negatively impact the formation of tissues and organs during development. In this review, we will discuss the teratogens linked to the development of many birth defects, with a strong focus on those that specifically affect the development of the NC, thereby producing neurocristopathies.Although increasing attention is being paid to the effect of teratogens on embryonic development in general, there is a strong need to critically evaluate the specific role of these agents in NC development. Therefore, increased understanding of the role of these factors in NC development will contribute to the planning of strategies aimed at the prevention and treatment of human neurocristopathies, whose etiology was previously not considered.

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Zika and the Eye: Pieces of a Puzzle

Cited by 34 publications

References 168 publications

Ocular Manifestations of Emerging Flaviviruses and the Blood-Retinal Barrier

Ocular Manifestations of Emerging Flaviviruses and the Blood-Retinal Barrier

Correlation between cephalic circumference at birth and ocular alterations in patients with microcephaly potentially associated with Zika Virus infection

The role of teratogens in neural crest development

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