FIGURE SUMMARY
Title

Oxidative Stress, Inflammation and Altered Glucose Metabolism Contribute to the Retinal Phenotype in the Choroideremia Zebrafish

Authors
Méjécase, C., Nair, N., Sarkar, H., Soro-Barrio, P., Toms, M., Halliday, S., Linkens, K., Jaroszynska, N., Maurer, C., Owen, N., Moosajee, M.
Source
Full text @ Antioxidants (Basel)
Figure 1

Cytokine pathway is upregulated in chmru848 zebrafish retina. chmru848 zebrafish samples are indicated in magenta and wt samples are indicated in cyan.
Figure 2

Oxidative (a), ER stress (b) and apoptosis (c) markers are upregulated in the chmru848 zebrafish retina. chmru848 zebrafish are indicated in magenta and wt samples are indicated in cyan.
Figure 3

Glycolysis is downregulated in favour of the pentose phosphate pathway in chmru848 zebrafish retina. (a,b) Glycolysis pathways are affected in chmru848 retina. (a) chmru848 zebrafish are indicated in magenta and wt samples are indicated in cyan. (b) Scheme adapted from https://www.wikipathways.org/instance/WP1356 (accessed on 18 December 2024) [27,28]. Significantly downregulated genes are indicated in blue, while upregulated genes are in red. (c) Pentose phosphate pathway is upregulated in the chmru848 retina compared to wt.
Figure 4

PFKM overexpression improves retinal phenotype but not photoreceptor cell death at 5 dpf. (a) Human PFKM expression was detected 5 days post-injection in chmru848 and wt zebrafish. (b) mRNA-injected chmru848 showed a more preserved photoreceptor layer (white asterisk) with better retinal lamination and a thicker RPE layer compared to the uninjected mutants (n = 9 zebrafish per group). Scale bar: 50 μm; scale bar zoom in: 20 μm. (c) Cell viability is unchanged after PFKM overexpression in wt and chmru848 zebrafish (n = 9 zebrafish per group). Scale bar = 50 μm. ONL: outer nuclear layer; INL: inner nuclear layer. (d,e) Expression of anti-apoptotic (d) and pro-apoptotic (e) markers were analysed using RT-qPCR at 5 dpf in zebrafish eyes, from uninjected and injected wt and chmru848. Data are expressed as mean ± SEM from n = 3 (with 20 eyes per group). Statistical significance was determined by one-way ANOVA. * p < 0.05; ** p < 0.005; **** p < 0.0001. “●”—wt; “▲”—wt + PFKM; “▼”—chmru848; “◆”—chmru848 + PFKM.

EXPRESSION / LABELING:
Genes:
Fish:
Anatomical Term:
Stage: Day 5
PHENOTYPE:
Fish:
Observed In:
Stage: Day 5
Figure 5

PFKM overexpression rescues 2-NBDG uptake in photoreceptors in chmru848 retina at 5 dpf. Scale bar = 50 μm. 2-NBDG is in green; nucleus stained with DAPI (blue). * p < 0.05; **** p < 0.0001.
Figure 6

PFKM overexpression does not improve activity of the glycolysis pathway or oxidative stress 5 dpf in chmru848 zebrafish. Expression of genes involved in the glycolysis pathway (a), in the pentose phosphate oxidative branch (b) and in oxidative stress (c) were analysed using RT-qPCR at 5dpf in zebrafish eyes, from uninjected and injected wt and chmru848. Data are expressed as mean ± SEM from n = 3 (with 20 eyes per group). Statistical significance was determined by One-way ANOVA. * p < 0.05; ** p < 0.005; *** p < 0.001; **** p < 0.0001. “●”—wt; “▲”—wt + PFKM; “▼”—chmru848; “◆”—chmru848 + PFKM.

EXPRESSION / LABELING:
Genes:
Fish:
Anatomical Term:
Stage: Day 5
PHENOTYPE:
Fish:
Observed In:
Stage: Day 5
Acknowledgments
This image is the copyrighted work of the attributed author or publisher, and ZFIN has permission only to display this image to its users. Additional permissions should be obtained from the applicable author or publisher of the image. Full text @ Antioxidants (Basel)
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