Loss of Stim2 in zebrafish induces glaucoma-like phenotype.

Autor: Baranykova S; Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology in Warsaw, Ks. Trojdena 4, 02-109, Warsaw, Poland., Gupta RK; Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology in Warsaw, Ks. Trojdena 4, 02-109, Warsaw, Poland.; Amity Institute of Neuropsychology & Neurosciences, Amity University, Noida, 201313, India., Kajdasz A; Institute of Bioorganic Chemistry, Polish Academy of Sciences, Zygmunta Noskowskiego 12/14, 61-704, Poznan, Poland.; Xenstats sp. z o.o., Otwarta 1, 60-008, Poznan, Poland., Wasilewska I; Mossakowski Medical Research Institute, Polish Academy of Sciences, Adolfa Pawińskiego 5, 02-106, Warsaw, Poland., Macias M; Microscopy and Cytometry Facility, International Institute of Molecular and Cell Biology, Ks. Trojdena 4, 02-109, WarsawWarsaw, Poland., Szybinska A; Microscopy and Cytometry Facility, International Institute of Molecular and Cell Biology, Ks. Trojdena 4, 02-109, WarsawWarsaw, Poland., Węgierski T; Microscopy and Cytometry Facility, International Institute of Molecular and Cell Biology, Ks. Trojdena 4, 02-109, WarsawWarsaw, Poland., Nahia KA; Laboratory of Zebrafish Developmental Genomics, International Institute of Molecular and Cell Biology in Warsaw, Ks. Trojdena 4, 02-109, Warsaw, Poland., Mondal SS; Laboratory of Zebrafish Developmental Genomics, International Institute of Molecular and Cell Biology in Warsaw, Ks. Trojdena 4, 02-109, Warsaw, Poland., Winata CL; Laboratory of Zebrafish Developmental Genomics, International Institute of Molecular and Cell Biology in Warsaw, Ks. Trojdena 4, 02-109, Warsaw, Poland., Kuźnicki J; Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology in Warsaw, Ks. Trojdena 4, 02-109, Warsaw, Poland., Majewski L; Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology in Warsaw, Ks. Trojdena 4, 02-109, Warsaw, Poland. lmajewski@iimcb.gov.pl.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Oct 18; Vol. 14 (1), pp. 24442. Date of Electronic Publication: 2024 Oct 18.
DOI: 10.1038/s41598-024-74909-0
Abstrakt: 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 Ca 2+ 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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