The Optokinetic Response as a Quantitative Measure of Visual Acuity in Zebrafish

Cameron, D. Joshua; Rassamdana, Faydim; Tam, Peony; Dang, Kathleen; Yáñez, Carolina; Ghaemmaghami, Saman; Dehkordi, Mahsa Iranpour

doi:10.3791/50832

Cited by 31 publications

(27 citation statements)

References 23 publications

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“…A reduction in functional vision is also seen, as evidenced by OKR, which has been proven to be a useful measure of visual acuity in zebrafish. 32,41 Using our OKR testing system, wild-type fish show a VA threshold of 1.395 cpd at 12 mpf, whereas mfrp −/− fish show a VA threshold of 3.922 cpd, a clear reduction in visual acuity likely caused by refractive error. The axial length of the mfrp eye is decreased when considered as a single metric, and also when normalized to an independent metric, such as the lens or the overall body length.…”

Section: Discussionmentioning

confidence: 96%

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Loss of Zebrafish Mfrp Causes Nanophthalmia, Hyperopia, and Accumulation of Subretinal Macrophages

Collery

Volberding

Bostrom

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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PurposeMutations in membrane frizzled-related protein (MFRP) are associated with nanophthalmia, hyperopia, foveoschisis, irregular patches of RPE atrophy, and optic disc drusen in humans. Mouse mfrp mutants show retinal degeneration but no change in eye size or refractive state. The goal of this work was to generate zebrafish mutants to investigate the loss of Mfrp on eye size and refractive state, and to characterize other phenotypes observed.MethodsClustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 methods were used to generate multiple frameshift mutations in zebrafish mfrp causing premature translational stops in Mfrp. Spectral-domain optical coherence tomography (SD-OCT) was used to measure eye metrics and refractive state, and immunohistochemistry was used to study adult eyes. Gene expression levels were measured using quantitative PCR.ResultsZebrafish Mfrp was shown to localize to apical and basal regions of RPE cells, as well as the ciliary marginal zone. Loss of Mfrp in mutant zebrafish was verified histologically. Zebrafish eyes that were mfrp mutant showed reduced axial length causing hyperopia, RPE folding, and macrophages were observed subretinally. Visual acuity was reduced in mfrp mutant animals.ConclusionsMutation of zebrafish mfrp results in hyperopia with subretinal macrophage infiltration, phenocopying aspects of human and mouse Mfrp deficiency. These mutant zebrafish will be useful in studying the onset and progression of Mfrp-related nanophthalmia, the cues that initiate the recruitment of macrophages, and the mechanisms of Mfrp function.

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Section: Discussionmentioning

confidence: 96%

“…Spatial frequencies were converted to cycles per degree (cpd) as previously described. 32 Contrast testing was carried out at a constant spatial frequency of 7.7 cpd, with settings ranging from 0 (no contrast, gray screen) to 5 (full contrast, black and white stripes).…”

Section: Methodsmentioning

confidence: 99%

Loss of Zebrafish Mfrp Causes Nanophthalmia, Hyperopia, and Accumulation of Subretinal Macrophages

Collery

Volberding

Bostrom

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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“…, Schmid & Wildsoet , Cameron et al . ) and other preliminary tools (Miller & Parisi ) to measure vision has been described, yet there is no “gold standard” measure of VA or visual function in dogs. Establishing validity of our test as a measure of VA is therefore difficult.…”

Section: Discussionmentioning

confidence: 99%

“…This pilot study suggests clinical use of a FPL task may be of similar use in dogs. The use of optokinetic nystagmus (Bloom & Berkley 1977, Ezeh et al 1990, Schmid & Wildsoet 1998, Cameron et al 2013) and other preliminary tools (Miller & Parisi 2018) to measure vision has been described, yet there is no "gold standard" measure of VA or visual function in dogs. Establishing validity of our test as a measure of VA is therefore difficult.…”

Section: Discussionmentioning

confidence: 99%

A forced‐choice preferential looking task for the assessment of vision in dogs: pilot study

Graham

Byosiere

Feng

et al. 2018

J of Small Animal Practice

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Objectives To describe preliminary use of a forced‐choice preferential looking task for the clinical assessment of vision in dogs. Materials and Methods The vision of 18 pet dogs was investigated in two separate studies using a forced‐choice preferential looking task: multiple observers watched eye, head and body movements on video recordings to identify cues suggesting when a dog had seen the feature of interest. Human observer reliability was determined using eight dogs and computer‐generated stimuli. Visual acuity was assessed using computer‐generated grating stimuli: in real‐time, an observer watched each dog's eye movement patterns and behaviour to decide whether each grating was seen. Stimuli were presented in a step‐wise manner and were controlled by the observer. Acuity was estimated as the highest spatial frequency the dog was determined to have seen. Results Median estimated visual acuity was better at 1 m compared to that at 3 m. Average test time was longer at a 3‐m distance than at 1 m. Inter‐ and intra‐observer reliability was better from 1 m than from 3 m. Clinical Significance Preliminary use of a forced‐choice preferential looking task for measurement of visual acuity in dogs has potential use as a clinical tool for the assessment of vision in dogs.

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“…[ 13 ] We previously developed a method to repeatedly and accurately utilize the optokinetic response (OKR) to measure and calculate visual acuity in adult zebrafish. [ 14 ] We hypothesized that a direct intracameral injection of zeaxanthin in anterior chamber will improve the visual acuity of the zebrafish over time. In this study, we injected zeaxanthin into the eyes of adult zebrafish and measured their visual acuity to observe whether zeaxanthin alone has a beneficial effect.…”

Section: Introductionmentioning

confidence: 99%

The Effect of Zeaxanthin on the Visual Acuity of Zebrafish

2015

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Oral supplementation of carotenoids such as zeaxanthin or lutein which naturally occur in human retina have been shown to improve vision and prevent progression of damage to advanced AMD in some studies. The zebrafish eye shares many physiological similarities with the human eye and is increasingly being used as model for vision research. We hypothesized that injection of zeaxanthin into the zebrafish eye would improve the visual acuity of the zebrafish over time. Visual acuity, calculated in cycles per degree, was measured in adult zebrafish to establish a consistent baseline using the optokinetic response. Zeaxanthin dissolved into phosphate buffered saline (PBS) or PBS only was injected into the anterior chamber of the right and left eyes of the Zebrafish. Visual acuities were measured at 1 week and 3, 8 and 12 weeks post-injection to compare to baseline values. Repeated measures ANOVA was used to compare visual acuities between fish injected with PBS and zeaxanthin. A significant improvement in visual acuity, 14% better than before the injection (baseline levels), was observed one week after injection with zeaxanthin (p = 0.04). This improvement peaked at more than 30% for some fish a few weeks after the injection and improvement in vision persisted at 3 weeks after injection (p = 0.006). The enhanced visual function was not significantly better than baseline at 8 weeks (p = 0.19) and returned to baseline levels 12 weeks after the initial injection (p = 0.50). Zeaxanthin can improve visual acuity in zebrafish eyes. Further studies are required to develop a better understanding of the role zeaxanthin and other carotenoids play during normal visual function.

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The Optokinetic Response as a Quantitative Measure of Visual Acuity in Zebrafish

Cited by 31 publications

References 23 publications

Loss of Zebrafish Mfrp Causes Nanophthalmia, Hyperopia, and Accumulation of Subretinal Macrophages

Loss of Zebrafish Mfrp Causes Nanophthalmia, Hyperopia, and Accumulation of Subretinal Macrophages

A forced‐choice preferential looking task for the assessment of vision in dogs: pilot study

The Effect of Zeaxanthin on the Visual Acuity of Zebrafish

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