Correspondence Between Behavioral, Physiological, and Anatomical Measurements of Visual Function in Inhibitory Neuron–Ablated Zebrafish

The zebrafish (Danio rerio) is a popular vertebrate model for studying visual development, especially at the larval stage. For many vertebrates, post-natal visual experience is essential to fine-tune visual development, but it is unknown how experience shapes larval zebrafish vision. Zebrafish swim with a moving texture; in the wild, this innate optomotor response (OMR) stabilises larvae in moving water, but it can be exploited in the laboratory to assess zebrafish visual function. Here, we compared spatial-frequency tuning inferred from OMR between visually naïve and experienced larvae from 5 to 7 days post-fertilisation. We also examined development of synaptic connections between neurons by quantifying post-synaptic density 95 (PSD-95) in larval retinae. PSD-95 is closely associated with N-methyl-D-aspartate (NMDA) receptors, the neurotransmitter-receptor proteins underlying experience-dependent visual development. We found that rather than following an experience-independent genetic programme, developmental changes in visual spatial-frequency tuning at the larval stage required visual experience. Exposure to motion evoking OMR yielded no greater improvement than exposure to static form, suggesting that increased sensitivity as indexed by OMR was driven not by motor practice but by visual experience itself. PSD-95 density varied with visual sensitivity, suggesting that experience may have up-regulated clustering of PSD-95 for synaptic maturation in visual development.

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“…The OMR apparatus was the same as described in our previous work 30 , adapted from one used by Orger and colleagues (Fig. 1a,b) 27 .…”

Section: Methodsmentioning

confidence: 99%

Experience-dependent development of visual sensitivity in larval zebrafish

Xie

Jusuf

Bui

et al. 2019

Sci Rep

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“…The OMR apparatus was adapted from that previously described (Xie et al, 2019a; Xie et al, 2021; Xie et al, 2019b). A Power Mac G5 computer (Apple Computer, Inc., Cupertino, CA, USA) ran MATLAB 2016b (MathWorks, Natick, MA, USA) with Psychtoolbox extensions (Kleiner et al, 2007).…”

Section: Methodsmentioning

confidence: 99%

EFEMP1 contributes to light-dependent ocular growth in zebrafish

Xie,

Bui,

Goodbourn

et al. 2023

Preprint

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Myopia (short-sightedness) is the most common ocular disorder. It generally develops after over-exposure to aberrant visual environments, disrupting emmetropization mechanisms that should match eye growth with optical power. A pre-screening of strongly associated myopia-risk genes identified through human genome-wide association studies implicatesefemp1in myopia development, but how this gene impacts ocular growth remains unclear. Here, we modifyefemp1expression specifically in the retina of zebrafish. We found that under normal lighting,efemp1mutants developed axial myopia, enlarged eyes, reduced spatial vision and altered retinal function. However, under myopia-inducing dark-rearing, compared to control fish, mutants remained emmetropic and showed changes in retinal function.Efemp1modification changed the expression ofefemp1,egr1,tgfb1a,vegfabandrbp3genes in the eye, and changes the inner retinal distributions of myopia-associated EFEMP1, TIMP2 and MMP2 proteins.Efemp1modification also impacted dark-rearing-induced responses ofvegfabandwnt2bgenes and above-mentioned myopia-associated proteins. Together, we provided robust evidence that light-dependent ocular growth is regulated byefemp1.SummaryThis study shows that retina-specific modification ofefemp1expression in zebrafish results in myopic eye, and impacts responses to myopia-inducing dark-rearing in eye growth, retinal function, and myopia-associated molecular expression and distribution, implicating light-dependent regulation ofefemp1in ocular development.

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“…The OMR apparatus was adapted from that previously described. [20][21][22] A Power Mac G5 computer (Apple Computer, Inc., Cupertino, CA, USA) ran MATLAB 2016b (MathWorks, Natick, MA, USA) with Psychtoolbox extensions. 23 Stimuli were processed on an ATI Radeon HD 5770 graphics card, with the output sent to a BITS++ video processor (Cambridge Research Systems, Rochester, UK) for increased contrast resolution for stimuli displayed on a M992 flat-screen cathode ray tube (CRT) monitor (Dell Computer Corporation, Round Rock, TX, USA) with its screen facing upwards.…”

Section: Optomotor Response (Omr)mentioning

confidence: 99%

Establishment and comprehensive characterization of a novel dark-reared zebrafish model for myopia studies

Xie,

Goodbourn,

Bui

et al. 2023

Preprint

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PurposeMyopia is predicted to impact approximately 5 billion people by 2050, necessitating mechanistic understanding of its development. Myopia results from dysregulated genetic mechanisms of emmetropization, caused by over-exposure to aberrant visual environments; however, these genetic mechanisms remain unclear. Recent human genome-wide association studies have identified a range of novel myopia-risk genes. To facilitate large-scalein vivomechanistic examination of gene-environment interactions, this study aims to establish a myopia model platform that allows efficient environmental and genetic manipulations.MethodsWe established an environmental zebrafish myopia model by dark-rearing. Ocular biometrics including relative ocular refraction were quantified using optical coherence tomography images. Spatial vision was assessed using optomotor response (OMR). Retinal function was analyzed via electroretinography (ERG). Myopia-associated molecular contents or distributions were examined using RT-qPCR or immunohistochemistry.ResultsOur model produces robust phenotypic changes, showing myopia after 2 weeks of dark-rearing, which were recoverable within 2 weeks after returning animals to normal lighting. 2-week dark-reared zebrafish have reduced spatial-frequency tuning function. ERG showed reduced photoreceptor and bipolar cell function (a- andb-waves) after only 2 days of dark-rearing, which worsened after 2 weeks of dark-rearing. We also found dark-rearing-induced changes to expression of myopia-risk genes, includingegr1, vegfaa, vegfab, rbp3, gjd2aandgjd2b, inner retinal distribution of EFEMP1, TIMP2 and MMP2, as well as transiently reduced PSD95 density in the inner plexiform layer.ConclusionsCoupled with the gene editing tools available for zebrafish, our environmental myopia model provides an excellent platform for large-scale investigation of gene-environment interactions in myopia development.

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Correspondence Between Behavioral, Physiological, and Anatomical Measurements of Visual Function in Inhibitory Neuron–Ablated Zebrafish

Cited by 11 publications

References 74 publications

Experience-dependent development of visual sensitivity in larval zebrafish

Experience-dependent development of visual sensitivity in larval zebrafish

EFEMP1 contributes to light-dependent ocular growth in zebrafish

Establishment and comprehensive characterization of a novel dark-reared zebrafish model for myopia studies

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