PUBLICATION

Loss of Stim2 in zebrafish induces glaucoma-like phenotype

Authors
Baranykova, S., Gupta, R.K., Kajdasz, A., Wasilewska, I., Macias, M., Szybinska, A., Węgierski, T., Nahia, K.A., Mondal, S.S., Winata, C.L., Kuźnicki, J., Majewski, L.
ID
ZDB-PUB-241020-8
Date
2024
Source
Scientific Reports   14: 2444224442 (Journal)
Registered Authors
Gupta, Rishikesh Kumar, Majewski, Lukasz, Szybinska, Aleksandra, Wasilewska, Iga, Winata, Cecilia Lanny
Keywords
GABAergic amacrine cells, Glaucoma, Retina, SOCE, Stim2, scRNA-seq
Datasets
GEO:GSE264312, GEO:GSE264310, GEO:GSE264309
MeSH Terms
  • Stromal Interaction Molecule 2*/genetics
  • Stromal Interaction Molecule 2*/metabolism
  • GABAergic Neurons/metabolism
  • GABAergic Neurons/pathology
  • Animals
  • Disease Models, Animal
  • Glaucoma*/genetics
  • Glaucoma*/metabolism
  • Glaucoma*/pathology
  • Superior Colliculi/metabolism
  • Superior Colliculi/pathology
  • Zebrafish*
  • Phenotype
  • Retina/metabolism
  • Retina/pathology
  • Calcium/metabolism
  • Gene Knockout Techniques
  • Zebrafish Proteins*/genetics
  • Zebrafish Proteins*/metabolism
  • Amacrine Cells/metabolism
  • Amacrine Cells/pathology
(all 21)
PubMed
39424970 Full text @ Sci. Rep.
Abstract
Calcium is involved in vision processes in the retina and implicated in various pathologies, including glaucoma. Rod cells rely on store-operated calcium entry (SOCE) to safeguard against the prolonged lowering of intracellular calcium ion concentrations. Zebrafish that lacked the endoplasmic reticulum Ca2+ sensor Stim2 (stim2 knockout [KO]) exhibited impaired vision and lower light perception-related gene expression. We sought to understand mechanisms that are responsible for vision impairment in stim2 KO zebrafish. The single-cell RNA (scRNA) sequencing of neuronal cells from brains of 5 days postfertilization larvae distinguished 27 cell clusters, 10 of which exhibited distinct gene expression patterns, including amacrine and γ-aminobutyric acid (GABA)ergic retinal interneurons and GABAergic optic tectum cells. Five clusters exhibited significant changes in cell proportions between stim2 KO and controls, including GABAergic diencephalon and optic tectum cells. Transmission electron microscopy of stim2 KO zebrafish revealed decreases in width of the inner plexiform layer, ganglion cells, and their dendrites numbers (a hallmark of glaucoma). GABAergic neuron densities in the inner nuclear layer, including amacrine cells, as well as photoreceptors significantly decreased in stim2 KO zebrafish. Our study suggests a novel role for Stim2 in the regulation of neuronal insulin expression and GABAergic-dependent vision causing glaucoma-like retinal pathology.
Genes / Markers
Figures
Figure Gallery (8 images)
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Expression
No data available
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
a4598TgTransgenic Insertion
    waw301
      Insertion
      waw303
        Small Deletion
        1 - 3 of 3
        Show
        Human Disease / Model
        No data available
        Sequence Targeting Reagents
        No data available
        Fish
        Antibodies
        Name Type Antigen Genes Isotypes Host Organism
        Ab7-rhomonoclonal
          IgG1Mouse
          1 - 1 of 1
          Show
          Orthology
          No data available
          Engineered Foreign Genes
          Marker Marker Type Name
          GCaMPEFGGCaMP
          1 - 1 of 1
          Show
          Mapping
          No data available