Evolution of ocular defects in infant macaques following in utero Zika virus infection
Congenital Zika syndrome (CZS) is associated with microcephaly and various neurological, musculoskeletal, and ocular abnormalities, but the long-term pathogenesis and postnatal progression of ocular defects in infants are not well characterized. Rhesus macaques are superior to rodents as models of C...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical investigation
2020-12-01
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| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.143947 |
| _version_ | 1818599951716843520 |
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| author | Glenn Yiu Sara M. Thomasy M. Isabel Casanova Alexander Rusakevich Rebekah I. Keesler Jennifer Watanabe Jodie Usachenko Anil Singapuri Erin E. Ball Eliza Bliss-Moreau Wendi Guo Helen Webster Tulika Singh Sallie Permar Amir Ardeshir Lark L. Coffey Koen K.A. Van Rompay |
| author_facet | Glenn Yiu Sara M. Thomasy M. Isabel Casanova Alexander Rusakevich Rebekah I. Keesler Jennifer Watanabe Jodie Usachenko Anil Singapuri Erin E. Ball Eliza Bliss-Moreau Wendi Guo Helen Webster Tulika Singh Sallie Permar Amir Ardeshir Lark L. Coffey Koen K.A. Van Rompay |
| author_sort | Glenn Yiu |
| collection | DOAJ |
| description | Congenital Zika syndrome (CZS) is associated with microcephaly and various neurological, musculoskeletal, and ocular abnormalities, but the long-term pathogenesis and postnatal progression of ocular defects in infants are not well characterized. Rhesus macaques are superior to rodents as models of CZS because they are natural hosts of the virus and share similar immune and ocular characteristics, including blood–retinal barrier characteristics and the unique presence of a macula. Using a previously described model of CZS, we infected pregnant rhesus macaques with Zika virus (ZIKV) during the late first trimester and characterized postnatal ocular development and evolution of ocular defects in 2 infant macaques over 2 years. We found that one of them exhibited colobomatous chorioretinal atrophic lesions with macular and vascular dragging as well as retinal thinning caused by loss of retinal ganglion neuron and photoreceptor layers. Despite these congenital ocular malformations, axial elongation and retinal development in these infants progressed at normal rates compared with healthy animals. The ZIKV-exposed infants displayed a rapid loss of ZIKV-specific antibodies, suggesting the absence of viral replication after birth, and did not show any behavioral or neurological defects postnatally. Our findings suggest that ZIKV infection during early pregnancy can impact fetal retinal development and cause congenital ocular anomalies but does not appear to affect postnatal ocular growth. |
| first_indexed | 2024-12-16T12:27:45Z |
| format | Article |
| id | doaj.art-2cd2489dc6de4c538a3e5cd3e3879e74 |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-12-16T12:27:45Z |
| publishDate | 2020-12-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-2cd2489dc6de4c538a3e5cd3e3879e742022-12-21T22:31:47ZengAmerican Society for Clinical investigationJCI Insight2379-37082020-12-01524Evolution of ocular defects in infant macaques following in utero Zika virus infectionGlenn YiuSara M. ThomasyM. Isabel CasanovaAlexander RusakevichRebekah I. KeeslerJennifer WatanabeJodie UsachenkoAnil SingapuriErin E. BallEliza Bliss-MoreauWendi GuoHelen WebsterTulika SinghSallie PermarAmir ArdeshirLark L. CoffeyKoen K.A. Van RompayCongenital Zika syndrome (CZS) is associated with microcephaly and various neurological, musculoskeletal, and ocular abnormalities, but the long-term pathogenesis and postnatal progression of ocular defects in infants are not well characterized. Rhesus macaques are superior to rodents as models of CZS because they are natural hosts of the virus and share similar immune and ocular characteristics, including blood–retinal barrier characteristics and the unique presence of a macula. Using a previously described model of CZS, we infected pregnant rhesus macaques with Zika virus (ZIKV) during the late first trimester and characterized postnatal ocular development and evolution of ocular defects in 2 infant macaques over 2 years. We found that one of them exhibited colobomatous chorioretinal atrophic lesions with macular and vascular dragging as well as retinal thinning caused by loss of retinal ganglion neuron and photoreceptor layers. Despite these congenital ocular malformations, axial elongation and retinal development in these infants progressed at normal rates compared with healthy animals. The ZIKV-exposed infants displayed a rapid loss of ZIKV-specific antibodies, suggesting the absence of viral replication after birth, and did not show any behavioral or neurological defects postnatally. Our findings suggest that ZIKV infection during early pregnancy can impact fetal retinal development and cause congenital ocular anomalies but does not appear to affect postnatal ocular growth.https://doi.org/10.1172/jci.insight.143947ImmunologyOphthalmology |
| spellingShingle | Glenn Yiu Sara M. Thomasy M. Isabel Casanova Alexander Rusakevich Rebekah I. Keesler Jennifer Watanabe Jodie Usachenko Anil Singapuri Erin E. Ball Eliza Bliss-Moreau Wendi Guo Helen Webster Tulika Singh Sallie Permar Amir Ardeshir Lark L. Coffey Koen K.A. Van Rompay Evolution of ocular defects in infant macaques following in utero Zika virus infection JCI Insight Immunology Ophthalmology |
| title | Evolution of ocular defects in infant macaques following in utero Zika virus infection |
| title_full | Evolution of ocular defects in infant macaques following in utero Zika virus infection |
| title_fullStr | Evolution of ocular defects in infant macaques following in utero Zika virus infection |
| title_full_unstemmed | Evolution of ocular defects in infant macaques following in utero Zika virus infection |
| title_short | Evolution of ocular defects in infant macaques following in utero Zika virus infection |
| title_sort | evolution of ocular defects in infant macaques following in utero zika virus infection |
| topic | Immunology Ophthalmology |
| url | https://doi.org/10.1172/jci.insight.143947 |
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