Using a variant of the optomotor response as a visual defect detection assay in zebrafish

LeFauve, Matthew K.; Rowe, Cassie J.; Crowley-Perry, Mikayla; Wiegand, Jenna L.; Shapiro, Arthur; Connaughton, Victoria P.

doi:10.14440/jbm.2021.341

Cited by 12 publications

(4 citation statements)

References 21 publications

(16 reference statements)

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“…S2C), all Top2 inhibitor–treated fish can feed normally and actively avoid capture, indicating that their vision is not substantially impaired. An optomotor response assay ( 29 ) showed no visual defects in 21 dpf fish that received embryonic treatment of flumequine and sodium salicylate, a Top2a-selective inhibitor (see more in the upcoming sections; fig. S2D).…”

Section: Resultsmentioning

confidence: 99%

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Top2a promotes the development of social behavior via PRC2 and H3K27me3

et al. 2022

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Little is understood about the embryonic development of sociality. We screened 1120 known drugs and found that embryonic inhibition of topoisomerase IIα (Top2a) resulted in lasting social deficits in zebrafish. In mice, prenatal Top2 inhibition caused defects in social interaction and communication, which are behaviors that relate to core symptoms of autism. Mutation of Top2a in zebrafish caused down-regulation of a set of genes highly enriched for genes associated with autism in humans. Both the Top2a-regulated and autism-associated gene sets have binding sites for polycomb repressive complex 2 (PRC2), a regulatory complex responsible for H3K27 trimethylation (H3K27me3). Moreover, both gene sets are highly enriched for H3K27me3. Inhibition of the PRC2 component Ezh2 rescued social deficits caused by Top2 inhibition. Therefore, Top2a is a key component of an evolutionarily conserved pathway that promotes the development of social behavior through PRC2 and H3K27me3.

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Section: Resultsmentioning

confidence: 99%

“…Optomotor response assay was conducted by following an established protocol ( 29 ). Briefly, five 21 dpf fish were placed in a 10-cm petri dish with a cylinder (two 50-ml tube caps taped together) placed in the middle.…”

Section: Methodsmentioning

confidence: 99%

Top2a promotes the development of social behavior via PRC2 and H3K27me3

et al. 2022

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“…Fish were allowed to acclimate for 30 s before stimulus presentation. The stimulus was a rotating black and white radial grating projected beneath the fish [ 27 ]. The stimulus first rotated clockwise for 30 s followed by 30 s of counterclockwise rotation, repeated twice.…”

Section: Methodsmentioning

confidence: 99%

Prolonged Hyperglycemia Causes Visual and Cognitive Deficits in Danio rerio

McCarthy

Dunn

Augustine

et al. 2022

IJMS

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The present study induced prolonged hyperglycemia (a hallmark symptom of Type 2 diabetes [T2DM]) in Danio rerio (zebrafish) for eight or twelve weeks. The goal of this research was to study cognitive decline as well as vision loss in hyperglycemic zebrafish. Fish were submerged in glucose for eight or twelve weeks, after which they were assessed with both a cognitive assay (three-chamber choice) and a visual assay (optomotor response (OMR)). Zebrafish were also studied during recovery from hyperglycemia. Here, fish were removed from the hyperglycemic environment for 4 weeks after either 4 or 8 weeks in glucose, and cognition and vision was again assessed. The 8- and 12-week cognitive results revealed that water-treated fish showed evidence of learning while glucose- and mannitol-treated fish did not within the three-day testing period. OMR results identified an osmotic effect with glucose-treated fish having significantly fewer positive rotations than water-treated fish but comparable rotations to mannitol-treated fish. The 8- and 12-week recovery results showed that 4 weeks was not enough time to fully recovery from the hyperglycemic insult sustained.

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“…Adults were removed from treatment tanks and placed individually in a 12-inch glass bowl placed on top of a 36-inch computer monitor (37,38). A 12-inch diameter rotating black and white radial grating stimulus was projected onto the monitor and rotated (clockwise and counterclockwise) with a control, gray screen in between.…”

Section: Optomotor Response (Omr)mentioning

confidence: 99%

Time dependent effects of prolonged hyperglycemia in zebrafish brain and retina

Rowe¹,

Delbridge‐Perry²,

Bonan³

et al. 2022

Front. Ophthalmol.

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Prolonged hyperglycemia causes long-term vision complications and an increased risk of cognitive deficits. High blood sugar also confers an osmotic load/stress to cells. We assessed behavioral and neurochemical changes in zebrafish brain and retina following prolonged hyperglycemia for 4-weeks or 8-weeks. At each time point, behavior was assessed using 3-chamber choice task and optomotor response; tissue was then collected and levels of inflammatory markers, tight junction proteins, and neurotransmitters determined using Western Blots. After 4-weeks, brain levels of v-rel reticuloendotheliosis viral oncogene homolog A (avian) (RelA; NF-kB subunit), IkB kinase (IKK), and glial fibrillary acidic protein (GFAP) were significantly elevated; differences in zonula occludens-1 (ZO-1), claudin-5, glutamic acid decarboxylase (GAD), and tyrosine hydroxylase (TH) were not significant. In retina, significant differences were observed only for TH (decreased), Rel A (increased), and GFAP (increased) levels. Glucose-specific differences in initial choice latency and discrimination ratios were also observed. After 8-weeks, RelA, GAD, and TH were significantly elevated in both tissues; IKK and GFAP levels were also elevated, though not significantly. ZO-1 and claudin-5 levels osmotically decreased in retina but displayed an increasing trend in glucose-treated brains. Differences in discrimination ratio were driven by osmotic load. OMRs increased in glucose-treated fish at both ages. In vivo analysis of retinal vasculature suggested thicker vessels after 4-weeks, but thinner vessels at 8-weeks. In vitro, glucose treatment reduced formation of nodes and meshes in 3B-11 endothelial cells, suggesting a reduced ability to form a vascular network. Overall, hyperglycemia triggered a strong inflammatory response causing initial trending changes in tight junction and neuronal markers. Most differences after 4-weeks of exposure were observed in glucose-treated fish suggesting effects on glucose metabolism independent of osmotic load. After 8-weeks, the inflammatory response remained and glucose-specific effects on neurotransmitter markers were observed. Osmotic differences impacted cognitive behavior and retinal protein levels; protein levels in brain displayed glucose-driven changes. Thus, we not only observed differential sensitivities of retina and brain to glucose-insult, but also different cellular responses, suggesting hyperglycemia causes complex effects at the cellular level and/or that zebrafish are able to compensate for the continued high blood glucose levels.

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Using a variant of the optomotor response as a visual defect detection assay in zebrafish

Cited by 12 publications

References 21 publications

Top2a promotes the development of social behavior via PRC2 and H3K27me3

Top2a promotes the development of social behavior via PRC2 and H3K27me3

Prolonged Hyperglycemia Causes Visual and Cognitive Deficits in Danio rerio

Time dependent effects of prolonged hyperglycemia in zebrafish brain and retina

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