June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Postnatal Development of ERG and VEP in Non-human Primates Exposed to Zika Virus
Author Affiliations & Notes
  • Jim Ver Hoeve
    Ophthalmology & Visual Science, University of Wisconsin, Madison, Wisconsin, United States
    OSOD, LLC, Madsison, Wisconsin, United States
  • T Michael Nork
    Ophthalmology & Visual Science, University of Wisconsin, Madison, Wisconsin, United States
    OSOD, LLC, Madsison, Wisconsin, United States
  • Charlene B Y Kim
    Ophthalmology & Visual Science, University of Wisconsin, Madison, Wisconsin, United States
    OSOD, LLC, Madsison, Wisconsin, United States
  • Carol A Rasmussen
    Ophthalmology & Visual Science, University of Wisconsin, Madison, Wisconsin, United States
    OSOD, LLC, Madsison, Wisconsin, United States
  • Thomas C Friederich
    Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, Wisconsin, United States
  • Matthew Aliota
    Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, Wisconsin, United States
  • Thaddeus C Golos
    Department of Obstetrics and Gynecology,, University of Wisconsin-Madison, Madison, Wisconsin, United States
  • David C O’Connor
    Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, Wisconsin, United States
  • Emma L Mohr
    Pediatrics, University of Wisconsin-Madison, Wisconsin, United States
  • Footnotes
    Commercial Relationships   Jim Ver Hoeve, None; T Michael Nork, None; Charlene Kim, None; Carol Rasmussen, None; Thomas Friederich, None; Matthew Aliota, None; Thaddeus Golos, None; David O’Connor, None; Emma Mohr, None
  • Footnotes
    Support  P01 AI132132 (DHO); R01 AI138647 (DHO); R01 AI116382-01A1S1 (DHO); K08 AI139341 (ELM); R01 AI132563 (MTA and TCF); Pediatric Infectious Diseases Society, Stanley A. Plotkin and Sanofi Pasteur (ELM); Clinical and Translational Science Award (CTSA) program, NIH National Center for Advancing Translational Sciences (NCATS), UL1TR002373-02 and TL1002375-02 (ELM); P30 EY016665 (TMN, JVH, CBYK, CAR); McPherson Eye Research Institute’s Retina Research Foundation Kathryn & Latimer Murfee (TMN); unrestricted grant from Research to Prevent Blindness to the University of Wisconsin Department of Ophthalmology and Visual Sciences (TMN, JVH, CBYK, CAR).
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 2239. doi:
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      Jim Ver Hoeve, T Michael Nork, Charlene B Y Kim, Carol A Rasmussen, Thomas C Friederich, Matthew Aliota, Thaddeus C Golos, David C O’Connor, Emma L Mohr; Postnatal Development of ERG and VEP in Non-human Primates Exposed to Zika Virus. Invest. Ophthalmol. Vis. Sci. 2020;61(7):2239.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : To describe the development of the light- and dark-adapted (LA, DA) electroretinogram (ERG) and flash cortical visual evoked potential (VEP) in neonatal non-human primates (NHP) as part of a study of the neurologic effects of maternal exposure to Zika virus (ZIKV).

Methods : Subjects were 16 rhesus macaque monkeys, age 5 - 90 days. Nine infants were exposed to ZIKV in utero; the rest served as controls. All animals underwent a complete ophthalmic examination and OCT imaging. For electrophysiologic testing, monkeys were anesthetized with propofol and pupils were dilated. Averages based on 5 or 80 flashes were recorded to 3.0 cd-s m-2 flashes. LA and DA intensity-response series were also recorded. Data were analyzed using a linear mixed effects analysis and comparisons were adjusted by corrected gestational age (covariate).

Results : As expected, no virus was detected in infants exposed in utero. The neonatal NHP LA ERG to a series of increasing flash strengths consisted of an A-wave and an early OP-like wave, with relatively constant implicit time (IT), followed by a B-wave, with ITs that increased exponentially with log flash strength, unlike the ‘photopic hill’ in adults. The DA ERG intensity series was relatively adult-like. The 5-flash average VEP from the youngest infants (<14 D, N=7) were of extraordinarily large amplitude (> 70 micro-volts) relative to infants 90 D old and adults. In contrast, young infant FVEP averages of 80 flashes became markedly diminished in amplitude and inconsistent relative to the same infant’s 5-flash average. OCT analyses found that the outer segment/interdigitation zone (OS/IZ) and the ONL were thinner and the IPL was thicker in ZIKV-exposed infants vs the controls. In general, neither ERG amplitudes nor fundus appearance distinguished ZIKV-exposed Infants from controls. However, one 30-day-old infant from a mother exposed to ZIKV in a previous pregnancy had a normal ERG but no recordable VEP and was behaviorally blind.

Conclusions : The NHP ERG and VEP undergo marked changes postnatally in both ZIKV-exposed infants and controls. The hyper-amplitude neonatal NHP VEP adapts rapidly and may not be evident with traditional averaging. The neonatal photopic B-wave IT is markedly delayed with increased flash strength. It is important to understand these postnatal changes in order to evaluate the effects of ZIKV exposure.

This is a 2020 ARVO Annual Meeting abstract.

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