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Relationship: 2375


A descriptive phrase which clearly defines the two KEs being considered and the sequential relationship between them (i.e., which is upstream, and which is downstream). More help

Altered, Visual function leads to Increased Mortality

Upstream event
The causing Key Event (KE) in a Key Event Relationship (KER). More help
Downstream event
The responding Key Event (KE) in a Key Event Relationship (KER). More help

Key Event Relationship Overview

The utility of AOPs for regulatory application is defined, to a large extent, by the confidence and precision with which they facilitate extrapolation of data measured at low levels of biological organisation to predicted outcomes at higher levels of organisation and the extent to which they can link biological effect measurements to their specific causes.Within the AOP framework, the predictive relationships that facilitate extrapolation are represented by the KERs. Consequently, the overall WoE for an AOP is a reflection in part, of the level of confidence in the underlying series of KERs it encompasses. Therefore, describing the KERs in an AOP involves assembling and organising the types of information and evidence that defines the scientific basis for inferring the probable change in, or state of, a downstream KE from the known or measured state of an upstream KE. More help

AOPs Referencing Relationship

AOP Name Adjacency Weight of Evidence Quantitative Understanding Point of Contact Author Status OECD Status
Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos) adjacent Brendan Ferreri-Hanberry (send email) Open for citation & comment
Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure adjacent Moderate Low Allie Always (send email) Open for citation & comment Under Review
Thyroperoxidase inhibition leading to altered visual function via decreased eye size adjacent Evgeniia Kazymova (send email) Under development: Not open for comment. Do not cite Under Development
Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning adjacent Cataia Ives (send email) Under development: Not open for comment. Do not cite Under Development

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KER.In general, this will be dictated by the more restrictive of the two KEs being linked together by the KER.  More help
Term Scientific Term Evidence Link
zebrafish Danio rerio High NCBI

Sex Applicability

An indication of the the relevant sex for this KER. More help
Sex Evidence
Unspecific Moderate

Life Stage Applicability

An indication of the the relevant life stage(s) for this KER.  More help
Term Evidence
All life stages Moderate

Key Event Relationship Description

Provides a concise overview of the information given below as well as addressing details that aren’t inherent in the description of the KEs themselves. More help

In animals, whatever the taxa, visual abilities are strongly linked to their lifestyle (feeding, avoidance of predators, movement, protection....). When these capacities are impaired, they lead to reduced fitness and are therefore strongly linked to a decrease in survival, particularly in the early stages of life.


Evidence Collection Strategy

Include a description of the approach for identification and assembly of the evidence base for the KER. For evidence identification, include, for example, a description of the sources and dates of information consulted including expert knowledge, databases searched and associated search terms/strings.  Include also a description of study screening criteria and methodology, study quality assessment considerations, the data extraction strategy and links to any repositories/databases of relevant references.Tabular summaries and links to relevant supporting documentation are encouraged, wherever possible. More help

Evidence Supporting this KER

Addresses the scientific evidence supporting KERs in an AOP setting the stage for overall assessment of the AOP. More help
Biological Plausibility
Addresses the biological rationale for a connection between KEupstream and KEdownstream.  This field can also incorporate additional mechanistic details that help inform the relationship between KEs, this is useful when it is not practical/pragmatic to represent these details as separate KEs due to the difficulty or relative infrequency with which it is likely to be measured.   More help

Decreases in visual functions can have a strong impact on behavior, leading to changes in individual response and abilities in the environment, including, for example, perception of food or avoidance of predators. Variation in the visual system can also influence learning tasks when visual stimuli are used (Corral-López et al., 2017). 

Sensory drive has been implicated in speciation in various taxa, largely based on phenotype-environment correlations and signatures of selection in sensory genes, including vision (Maan et al, 2017). 

It is biologically plausible that an animal which has difficulties in finding food and avoiding predators will have lower survival chances in wildlife.

Uncertainties and Inconsistencies
Addresses inconsistencies or uncertainties in the relationship including the identification of experimental details that may explain apparent deviations from the expected patterns of concordance. More help

It is obvious that impaired vision leads to higher mortality, as the sense of sight is important for survival, and if it is impaired, feeding or escape becomes more difficult. However, the number of studies investigating this connection is limited. It is often unclear to what extent this relationship is determined by altered visual function versus other pathways such as alterations in muscle development or other factors contributing to these types of behaviour. Also, the natural conditions, which depend on many variables, are difficult to reproduce in the laboratory or to compare between different laboratories. 

Known modulating factors

This table captures specific information on the MF, its properties, how it affects the KER and respective references.1.) What is the modulating factor? Name the factor for which solid evidence exists that it influences this KER. Examples: age, sex, genotype, diet 2.) Details of this modulating factor. Specify which features of this MF are relevant for this KER. Examples: a specific age range or a specific biological age (defined by...); a specific gene mutation or variant, a specific nutrient (deficit or surplus); a sex-specific homone; a certain threshold value (e.g. serum levels of a chemical above...) 3.) Description of how this modulating factor affects this KER. Describe the provable modification of the KER (also quantitatively, if known). Examples: increase or decrease of the magnitude of effect (by a factor of...); change of the time-course of the effect (onset delay by...); alteration of the probability of the effect; increase or decrease of the sensitivity of the downstream effect (by a factor of...) 4.) Provision of supporting scientific evidence for an effect of this MF on this KER. Give a list of references.  More help

Increase according to global health of the population (e.g on trout (Post and Parkinson, 2001)

Response-response Relationship
Provides sources of data that define the response-response relationships between the KEs.  More help
Information regarding the approximate time-scale of the changes in KEdownstream relative to changes in KEupstream (i.e., do effects on KEdownstream lag those on KEupstream by seconds, minutes, hours, or days?). More help
Known Feedforward/Feedback loops influencing this KER
Define whether there are known positive or negative feedback mechanisms involved and what is understood about their time-course and homeostatic limits. More help

Domain of Applicability

A free-text section of the KER description that the developers can use to explain their rationale for the taxonomic, life stage, or sex applicability structured terms. More help

Taxonomic applicability: The visual system of the fish (e.g., zebrafish) follows the typical organisation of vertebrates and is often used as a model to study human eye diseases. Although there are some differences, it is plausible to assume that visual function is important for survival across all vertebrates and invertebrates that have eyes.

Sex applicability: Zebrafish are undifferentiated gonochorists since both sexes initially develop an immature ovary (Maack and Segner, 2003). Immature ovary development progresses until approximately the onset of the third week. Later, in female fish immature ovaries continue to develop further, while male fish undergo transformation of ovaries into testes. Final transformation into testes varies among male individuals, however finishes usually around 6 weeks post fertilization. Effects on mortality resulting from altered visual function are therefore expected to be independent of sex.

Life stage applicability: It is plausible to assume that altered visual function of the eye would result in a higher mortality across all life stages. This could be especially true for the embryonic stages, the most sensitive stage of life. Vision plays a crucial role (in the early life stages) of most species, as eye development and establishment of functional vision is essential for perception of food or avoidance of predators for example (Carvalho et al., 2002).


List of the literature that was cited for this KER description. More help

Babkiewicz, E., Bazała, M., Urban, P., Maszczyk, P., Markowska, M., & Maciej Gliwicz, Z. (2020). The effects of temperature on the proxies of visual detection of Danio rerio larvae: observations from the optic tectum. Biology Open, 9(7).

Besson, M., Feeney, W. E., Moniz, I., François, L., Brooker, R. M., Holzer, G., Metian, M., Roux, N., Laudet, V., & Lecchini, D. (2020). Anthropogenic stressors impact fish sensory development and survival via thyroid disruption. Nature Communications, 11(1).

Brown, S. B., Adams, B. A., Cyr, D. G., & Eales, J. G. (2004). Contaminant effects on the teleost fish thyroid. Environmental Toxicology and Chemistry, 23(7), 1680–1701.

Carvalho, P. S. M., Noltie, D. B., & Tillitt, D. E. (2002). Ontogenetic improvement of visual function in the medaka Oryzias latipes based on an optomotor testing system for larval and adult fish. Animal Behaviour, 64(1), 1–10.

Corral-López, A., Garate-Olaizola, M., Buechel, S. D., Kolm, N., & Kotrschal, A. (2017). On the role of body size, brain size, and eye size in visual acuity. Behavioral Ecology and Sociobiology, 71(12).

Dehnert, G. K., Karasov, W. H., & Wolman, M. A. (2019). 2,4-Dichlorophenoxyacetic acid containing herbicide impairs essential visually guided behaviors of larval fish. Aquatic Toxicology, 209(October 2018), 1–12.

Flamarique IN. 2013. Opsin switch reveals function of the ultraviolet cone in fish foraging. Proceedings of the Royal Society B-Biological Sciences 280(1752).

Fuiman LA, Rose KA, Cowan JH, Smith EP. 2006. Survival skills required for predator evasion by fish larvae and their relation to laboratory measures of performance. Animal Behaviour 71:1389-1399.

Heijlen M, Houbrechts A, Bagci E, Van Herck S, Kersseboom S, Esguerra C, Blust R, Visser T, Knapen D, Darras V. 2014. Knockdown of type 3 iodothyronine deiodinase severely perturbs both

Houbrechts AM, Delarue J, Gabriels IJ, Sourbron J, Darras VM. 2016. Permanent Deiodinase Type 2 Deficiency Strongly Perturbs Zebrafish Development, Growth, and Fertility. Endocrinology 157(9):3668-3681.