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Loss of Stim2 in zebrafish induces retinal gene expression cellular changes resembling glaucoma characteristics [scRNA-seq]

ABSTRACT: Loss of Stim2 in zebrafish induces retinal gene expression cellular changes resembling glaucoma characteristics [scRNA-seq]

PROVIDER: PRJNA1101946 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28735563_1.fastq.gz	Fastqsanger.gz
	SRR28735563_2.fastq.gz	Fastqsanger.gz
	SRR28735564_1.fastq.gz	Fastqsanger.gz
	SRR28735564_2.fastq.gz	Fastqsanger.gz
	SRR28735565_1.fastq.gz	Fastqsanger.gz

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Loss of Stim2 in zebrafish induces retinal gene expression cellular changes resembling glaucoma characteristics [RNA-seq]

Project description:Calcium is involved in vision processes in retina and is implicated in various pathologies including glaucoma. Rods are protected against prolonged lowering of intracellular calcium ion concentrations by Store Operated Calcium Entry (SOCE). We showed zebrafish lacking SOCE calcium sensor Stim2 had problem with vision as indicated by behavior tests, staining of retina and downregulation of genes related to light perception. In this work we aimed to understand the mechanism responsible for the vision problems in stim2 zebrafish knockout. scRNA-sequencing of neuronal origin cells from brains of 5 dpf larvae identified 27 clusters. Differently expressed genes were detected in ten clusters including amacrine and GABAergic retinal interneurons and GABAergic optic tectum cells. In five clusters the proportion of cells in stim2 KO fish versus control was significantly decreased including GABAergic diencephalon and optic tectum, and was increased in amacrine and GABAergic retinal interneurons. Transmission Electron Microscopy in stim2 KO fish revealed decrease in width of inner plexiform layer (IPL), ganglion cells and their dendrites numbers what is characteristic for glaucoma. Analysis of cell density in the inner nucleus layer, which includes amacrine cells among others, showed a significant decrease in the number of GABAergic neurons. The area of cristae in photoreceptor mitochondria was statistically lower in stim2 KO than in control retinas.

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Loss of Stim2 in zebrafish induces retinal gene expression cellular changes resembling glaucoma characteristics [scRNA-seq]

Project description:Calcium is involved in vision processes in retina and is implicated in various pathologies including glaucoma. Rods are protected against prolonged lowering of intracellular calcium ion concentrations by Store Operated Calcium Entry (SOCE). We showed zebrafish lacking SOCE calcium sensor Stim2 had problem with vision as indicated by behavior tests, staining of retina and downregulation of genes related to light perception. In this work we aimed to understand the mechanism responsible for the vision problems in stim2 zebrafish knockout. scRNA-sequencing of neuronal origin cells from brains of 5 dpf larvae identified 27 clusters. Differently expressed genes were detected in ten clusters including amacrine and GABAergic retinal interneurons and GABAergic optic tectum cells. In five clusters the proportion of cells in stim2 KO fish versus control was significantly decreased including GABAergic diencephalon and optic tectum, and was increased in amacrine and GABAergic retinal interneurons. Transmission Electron Microscopy in stim2 KO fish revealed decrease in width of inner plexiform layer (IPL), ganglion cells and their dendrites numbers what is characteristic for glaucoma. Analysis of cell density in the inner nucleus layer, which includes amacrine cells among others, showed a significant decrease in the number of GABAergic neurons.The area of cristae in photoreceptor mitochondria was statistically lower in stim2 KO than in control retinas.

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Loss of Stim2 in zebrafish induces retinal gene expression cellular changes resembling glaucoma characteristics.

Project description:Loss of Stim2 in zebrafish induces retinal gene expression cellular changes resembling glaucoma characteristics.

| PRJNA1101942 | ENA

Loss of Stim2 in zebrafish induces retinal gene expression cellular changes resembling glaucoma characteristics [RNA-seq]

Project description:Loss of Stim2 in zebrafish induces retinal gene expression cellular changes resembling glaucoma characteristics [RNA-seq]

| PRJNA1101945 | ENA

Loss of Stim2 in zebrafish induces retinal gene expression cellular changes resembling glaucoma characteristics.

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APOE4 retinal microglia remain homeostatic in glaucoma.

Project description:The apolipoprotein E4 (APOE4) allele is associated with an increased risk of Alzheimer’s disease and a decreased risk of glaucoma, but the underlying mechanisms remain poorly understood. Here we find that in two mouse glaucoma models and in human glaucomatous retinas, microglia transition to a neurodegenerative (MGnD) phenotype characterized by upregulation of Apoe and Lgals3 (Galectin-3). Mice in which Apoe was targeted in microglia or carrying the human APOE4 allele were protected from retinal ganglion cell (RGC) loss despite elevated intraocular pressure (IOP). Similar to Apoe–/– retinal microglia, APOE4 microglia did not upregulate MGnD genes, including Lgals3, following IOP elevation. Genetic and pharmacologic targeting of Galectin-3 ameliorated RGC degeneration, and Galectin-3 expression was attenuated in human APOE4 glaucoma samples. These results demonstrate that impaired activation of APOE4 microglia is protective in glaucoma, and that the APOE-Galectin-3 signaling pathway can be targeted to treat this blinding disease.

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Retinal microglia transition to a neurodegenerative MGnD phenotype in glaucoma.

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