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. 2022 Sep 1;11:e77775. doi: 10.7554/eLife.77775

Figure 7. The synaptic vesicle cycle is a major contributor to hair-cell oxidative stress.

Figure 7.

(A) Average dot plots show the percentage of cells surviving neomycin treatment per neuromast. A significantly higher percentage of cells survive in otofb-/- mutants (orange) compared to siblings (black) when animals are treated with 0.1% DMSO for 24 hr from 4 to 5 dpf. No additional protection is observed in otofb-/- mutants (open orange) compared to siblings (open black) when animals are treated with 10 µM isradipine for 24 hr from 4 to 5 dpf prior to neomycin challenge. (B) Cartoon schematic of a hair cell with black box around the ribbon (magenta) synapse. (C) Close up of synapse demarcated in (B). Both presynaptic calcium influx (blue) and otoferlin (orange) function consume ATP (red stars) and stimulate ROS (yellow box) production. Blocking calcium influx inhibits both processes and reduces ROS levels. Blocking the synaptic vesicle cycle alone reduces ROS levels to a similar extent as the calcium channel block. Each dot in A represents one neuromast. A minimum of three animals were examined per treatment group. Error bars: SEM. For comparisons, a two-way ANOVA with a Sidak’s correction for multiple comparisons was used in A. * p<0.05.

Figure 7—source data 1. Mean numbers and statistics ototoxicity analyses.