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Relationship: 2375

Title

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

Altered, Visual function

Downstream event

The responding Key Event (KE) in a Key Event Relationship (KER). More help

Increased Mortality

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	EAGMST 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 Do not cite	Under Development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 Do not cite	Under Development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 Map 2.0

ID	Experimental Design	Species	Upstream Observation	Downstream Observation	Citation (first author, year)	Notes

Evidence Map

Addresses the scientific evidence supporting KERs in an AOP setting the stage for overall assessment of the AOP. More help

Title	First Author	Biological Plausibility	Dose Concordance	Temporal Concordance	Incidence Concordance

Biological Plausibility

Dose Concordance Evidence

Temporal Concordance Evidence

Incidence Concordance Evidence

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)

Quantitative Understanding of the Linkage

Captures information that helps to define how much change in the upstream KE, and/or for how long, is needed to elicit a detectable and defined change in the downstream KE. More help

Response-response Relationship

Provides sources of data that define the response-response relationships between the KEs. More help

Time-scale

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).