Ocular teratogens: old acquaintances and new dangers

Tandon, Anupama; Mulvihill, Alan

doi:10.1038/eye.2009.30

Cited by 14 publications

(10 citation statements)

References 43 publications

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“…In this analysis, we observed that ocular teratogens in all three species were those that significantly correlated with inflammatory signals, extracellular matrix remodeling, axonal guidance (most likely migratory cues), mitotic arrest, and the transporter ABCB1 (ATP-binding cassette subfamily B member 1). From the literature, mammalian ocular teratogens have been linked with neurogenesis from the Gene Ontology Biological Process, extracellular matrix remodeling, and mitotic arrest (Nemeth et al, 2005;Green et al, 2007;Tandon and Mulvihill, 2009). ABC transporters have been linked with neurogenesis, as well as neural stem cells and MESC toxicity (Lin et al, 2006;Chandler et al, 2011).…”

Section: Developmental Eye Defects: a Case Examplementioning

confidence: 99%

Zebrafish—As an integrative model for twenty‐first century toxicity testing

Sipes

Padilla

Knudsen

2011

Birth Defects Research Pt C

258

152

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The zebrafish embryo is a useful small model for investigating vertebrate development because of its transparency, low cost, transgenic and morpholino capabilities, conservation of cell signaling, and concordance with mammalian developmental phenotypes. From these advantages, the zebrafish embryo has been considered as an alternative model for traditional in vivo developmental toxicity screening. The use of this organism in conjunction with traditional in vivo developmental toxicity testing has the potential to reduce cost and increase throughput of testing the chemical universe, prioritize chemicals for targeted toxicity testing, generate predictive models of developmental toxicants, and elucidate mechanisms and adverse outcome pathways for abnormal development. This review gives an overview of the zebrafish embryo for pre dictive toxicology and 21st century toxicity testing. Developmental eye defects were selected as an example to evaluate data from the U.S. Environmental Protection Agency's ToxCast program comparing responses in zebrafish embryos with those from pregnant rats and rabbits for a subset of 24 environmental chemicals across >600 in vitro assay targets. Cross-species comparisons implied a common basis for biological pathways associated with neuronal defects, extracellular matrix remodeling, and mitotic arrest.

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Section: Developmental Eye Defects: a Case Examplementioning

confidence: 99%

Zebrafish—As an integrative model for twenty‐first century toxicity testing

Sipes

Padilla

Knudsen

2011

Birth Defects Research Pt C

258

152

View full text Add to dashboard Cite

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“…In the present study, embryos exposed to 8 mg DCA/L experienced !30% decreases in eye size index, suggesting that neurodevelopment may have been altered. Furthermore, reductions in eye size have been linked to altered brain development in zebrafish (Malicki et al 1996), and ocular teratogens have been linked to alterations in neurogenesis in mammals (Tandon and Mulvihill 2009). However, additional research is needed to fully understand the long-term implications of delayed or impaired neurological development in fathead minnow embryos and to determine whether alterations in eye size are a suitable FIGURE 5: Average eye area at 76 (A) and 96 (B) hours post fertilization (hpf) and average eye size index (eye area/snout-vent length) at 120 hpf (C) of embryos exposed to 3,4-dichloroaniline (DCA).…”

Section: Experiments 2: Responsiveness Of Potential Sublethal Fet Testmentioning

confidence: 99%

Development of cardiovascular and neurodevelopmental metrics as sublethal endpoints for the Fish embryo toxicity test

Krzykwa

Olivas

Jeffries

2018

Enviro Toxic and Chemistry

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The fathead minnow fish embryo toxicity (FET) test has been proposed as a more humane alternative to current toxicity testing methods as younger organisms are thought to experience less distress during toxicant exposure. However, the FET test protocol does not include endpoints that allow for the prediction of sublethal adverse outcomes, limiting its utility relative to other test types. Researchers have proposed the development of sublethal endpoints for the FET test to increase its utility. The present study 1) developed methods for previously unmeasured sublethal metrics in fathead minnows (i.e., spontaneous contraction frequency and heart rate) and 2) investigated the responsiveness of several sublethal endpoints related to growth (wet wt, length, and growth-related gene expression), neurodevelopment (spontaneous contraction frequency, eye size, and neurodevelopmental gene expression), and cardiovascular function and development (pericardial area, heart rate, and cardiovascular system-related gene expression) as additional FET test metrics using the model toxicant 3,4-dichloroaniline. Of the growth, neurological, and cardiovascular endpoints measured, length, eye size, and pericardial area were found to be more responsive than the other endpoints evaluated. Future studies linking alterations in these endpoints to longer-term adverse impacts are needed to fully evaluate the predictive power of these metrics in chemical and whole-effluent toxicity testing. Environ Toxicol Chem 2018;37:2530-2541. © 2018 SETAC.

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“…Retinal development is very sensitive to teratogen exposure [ 28 ]. Previous studies using zebrafish showed that embryonic ethanol exposure produced severe retinal cell differentiation defects [ 29 – 31 ], including reduced photoreceptor differentiation and optic nerve hypoplasia [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

Retinal Wnt signaling defect in a zebrafish fetal alcohol spectrum disorder model

Muralidharan

Sarmah

2018

PLoS ONE

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Fetal alcohol spectrum disorder caused by prenatal alcohol exposure includes ocular abnormalities (microphthalmia, photoreceptor dysfunction, cataracts). Zebrafish embryos exposed to ethanol from gastrulation through somitogenesis show severe ocular defects, including microphthalmia and photoreceptor differentiation defects. Ethanol-treated zebrafish had an enlarged ciliary marginal zone (CMZ) relative to the retina size and reduced Müller glial cells (MGCs). Ethanol exposure produced immature photoreceptors with increased proliferation, indicating cell cycle exit failure. Signaling mechanisms in the CMZ were affected by embryonic ethanol exposure, including Wnt signaling in the CMZ, Notch signaling and neurod gene expression. Retinoic acid or folic acid co-supplementation with ethanol rescued Wnt signaling and retinal differentiation. Activating Wnt signaling using GSK3 inhibitor (LSN 2105786; Eli Lilly and Co.) restored retinal cell differentiation pathways. Ethanol exposed embryos were treated with Wnt agonist, which rescued Wnt-active cells in the CMZ, Notch-active cells in the retina, proliferation, and photoreceptor terminal differentiation. Our results illustrate the critical role of Wnt signaling in ethanol-induced retinal defects.

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Ocular teratogens: old acquaintances and new dangers

Cited by 14 publications

References 43 publications

Zebrafish—As an integrative model for twenty‐first century toxicity testing

Zebrafish—As an integrative model for twenty‐first century toxicity testing

Development of cardiovascular and neurodevelopmental metrics as sublethal endpoints for the Fish embryo toxicity test

Retinal Wnt signaling defect in a zebrafish fetal alcohol spectrum disorder model

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