Pathogenesis and Manifestations of Zika Virus-Associated Ocular Diseases
Abstract
:1. Introduction
2. Virology
3. Host–Virus Interaction
3.1. Innate Immune Response to ZIKV Infection
3.2. T Cell-Mediated Immune Response to ZIKV Infection
3.3. Antibody-Mediated Immune Response to ZIKV Infection
4. Ocular Manifestations
5. Pathological Mechanisms
5.1. Blood–Tissue Barriers
5.2. ZIKV-Infected Myeloid Cells
5.3. Microcephaly
5.4. Placental Dysfunction
5.5. Congenital Zika Syndrome
5.6. Acute ZIKV Infection
5.6.1. Retina
5.6.2. Cornea
5.6.3. Trabecular Meshwork
5.6.4. Conjunctiva
5.6.5. Anterior Uvea
6. Conclusions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Anterior Segment | Neuro-Ophthalmic | Posterior Segment |
---|---|---|
Nonpurulent conjunctivitis [62]. Anterior uveitis (bilateral, nongranulomatous iridocyclitis with or without elevated intraocular pressure [57,64]. | Papilledema [66]. Ophthalmoplegia [5,66]. Ocular flutter [67]. | Maculopathy with outer retinal layer and RPE disruption [57,61]. Multifocal choroiditis [65]. |
Anterior Segment | Neuro-Ophthalmic | Posterior Segment |
---|---|---|
Lens subluxation [61,63]. Cataract [63,76,78]. Intraocular calcifications [63,76,78]. Congenital glaucoma [80] Microphthalmia [81,82]. Corneal ectasia [83]. Iris coloboma [63,84]. | Strabismus [79,85]. Horizontal nystagmus [79,85]. Exophoria/esophoria [79,85]. Loss of pupillary response [79,85]. Disc hypoplasia [79,85]. Disc pallor [79,85]. Enlarged cup-to-disc ratio [79,85]. | Macular pigment mottling [5,79]. Chorioretinal atrophy either macular, paramacular, or peripheral [5,79]. Retinal hemorrhage [86]. Vascular tortuosity [85]. Early termination of retinal vasculature [85]. Washed out peripheral retina with hypoluscent spot [85]. Photoreceptor, RPE thinning with pigment loss, and choroidal thinning [87,88]. |
Primary Targets | Receptors | Mechanisms | Outcomes |
---|---|---|---|
Neural progenitor cells | AXL [99]. | Apoptosis of ZIKV-infected NPCs. Reduced proliferation of NPCs. Premature differentiation of NPCs [113,115]. | Microcephaly [115]. |
Neural crest cells | AXL [100]. | ZIKV infection of NCCs during the developmental stages of the fetus causes abnormal migration, proliferation, and differentiation of NCCs [100,120]. The loss of NCCs associated with ZIKV infection can contribute to the disruption of the formation of the optic fissure, resulting in failure to close the optic fissure [86,120]. ZIKV infection of NCCs will result in abnormal proliferation and differentiation of cells required for the normal development of the cornea [121]. ZIKV infection of NCCs during the developmental stages of the fetus can lead to abnormal morphogenesis of the trabecular meshwork [100,122,123]. | Microphthalmia [106,120,124,125]. Iris coloboma [7,84,120,126]. Corneal ectasia [83]. Congenital glaucoma [93,100,122,123]. |
Mesenchymal stem cells | AXL [101]. | ZIKV infects mesenchymal stem cells, resulting in impaired proliferation and differentiation of cells required for the development of the crystalline lens [30,100,121,127,128]. | Congenital cataract [30,100,121,127,128]. |
Placental endothelial cells and trophoblasts | TIM-1, AXL, TYRO3 [27]. | Destruction of ZIKV-infected placenta [129,130]. Compromised maternal-fetal interface [129,130]. | Placental insufficiency causes restricted growth of the fetus and disruption of neurodevelopment of the fetus [129]. Facilitate access of ZIKV to the fetus [129,130]. |
Blood retinal barrier cells (Retinal vascular endothelial cells and retinal pigment epithelial cells) | AXL, TYRO3, TIM-1, RIG-I/MDA5, TLR3 [20]. | ZIKV infected BRB cells induce inflammation that damages the BRB and facilitate influx of effector immune cells into the retina [131,132]. | Chorioretinitis, macular pigment mottling, chorioretinal atrophy, and maculopathy [131,132]. |
Cornea epithelial cells | TLR3, RIG-I, MDA5 [133]. | ZIKV-infected corneal epithelium induces antiviral response and immune-mediated inflammation [133]. | Keratitis [133]. |
Trabecular meshwork cells | RIG-I, TLR3 [134]. | ZIKV-infected trabecular meshwork cells secrete cytokines and chemokines that promote inflammation via the recruitment of effector immune cells such as Th1 cells to the trabecular meshwork [134]. | Trabeculitis [134]. |
Conjunctival epithelial cells | RIG-I/MDA5, TLR3 [135]. | ZIKV-infected conjunctival epithelial cells induce an immune-mediated inflammatory response [135]. | Nonpurulent conjunctivitis [135]. |
Iris pigment epithelium | TLR3 [136]. | Immune-mediated inflammation triggered in response to ZIKV-infected iris pigment epithelium. ZIKV-infected blood aqueous barrier (BAB) cells induce inflammation that damages the BAB and facilitate influx of effector immune cells into the anterior uvea. Influx of ZIKV-infected monocytes acting as Trojan horses [137,138,139]. | Anterior uveitis with or without raised intraocular pressure [137,138,139]. |
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Labib, B.A.; Chigbu, D.I. Pathogenesis and Manifestations of Zika Virus-Associated Ocular Diseases. Trop. Med. Infect. Dis. 2022, 7, 106. https://doi.org/10.3390/tropicalmed7060106
Labib BA, Chigbu DI. Pathogenesis and Manifestations of Zika Virus-Associated Ocular Diseases. Tropical Medicine and Infectious Disease. 2022; 7(6):106. https://doi.org/10.3390/tropicalmed7060106
Chicago/Turabian StyleLabib, Bisant A., and DeGaulle I. Chigbu. 2022. "Pathogenesis and Manifestations of Zika Virus-Associated Ocular Diseases" Tropical Medicine and Infectious Disease 7, no. 6: 106. https://doi.org/10.3390/tropicalmed7060106