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:GSE264309, GEO:GSE264310
- MeSH Terms
-
- Phenotype
- Disease Models, Animal
- Retina/metabolism
- Retina/pathology
- Glaucoma*/genetics
- Glaucoma*/metabolism
- Glaucoma*/pathology
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- Zebrafish*
- Animals
- Gene Knockout Techniques
- Stromal Interaction Molecule 2*/genetics
- Stromal Interaction Molecule 2*/metabolism
- Superior Colliculi/metabolism
- Superior Colliculi/pathology
- Amacrine Cells/metabolism
- Amacrine Cells/pathology
- Calcium/metabolism
- GABAergic Neurons/metabolism
- GABAergic Neurons/pathology
- PubMed
- 39424970 Full text @ Sci. Rep.
Citation
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. (2024) Loss of Stim2 in zebrafish induces glaucoma-like phenotype. Scientific Reports. 14:2444224442.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping