Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Wildtype (wt) mouse cone transcriptome change with Txnip treatment

ABSTRACT: Purpose: To identifiy mRNA changes in wt cone photoreceptors with Txnip overexpression treatment, which improved retinitis pigmentosa (RP) cone survival and visual acuity. Methods: two wt mouse strains, BALB/c and C57BL/6J were injected with AAV-Txnip or AAV-H2BGFP control subretinally at P0. Retinas were dissected out at P21 for BALB/c and P35 for C57BL/6J. 1,000 H2BGFP labeled cones per retina sample were FACS sorted out, and subject for RNA-sequencing. Results: only ~70 genes in P21 BALB/c and 1 genes in C57BL/6J were found differentially expressed with Txnip treatment. Only 1 genes (i.e. Txnip) were in commonly upregulated between the two lists. Conclusions: Txnip seems to be not changing RNA expression much in wt cones. Instead, its major function to rescue RP cones may lay in protein-protein interactions.

ORGANISM(S): Mus musculus

PROVIDER: GSE168503 | GEO | 2021/03/15

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

Similar Datasets

Retinitis pigmentosa (RP) mouse cone transcriptom change with Txnip treatment

Project description:Purpose: To identifiy mRNA changes in retinitis pigmentosa (RP) cone photoreceptors with Txnip overexpression treatment, which improved RP cone survival and visual acuity. Methods: two RP mouse strains, rd1 and Rho-/-, were injected with AAV-Txnip or AAV-H2BGFP control subretinally at P0. Retinas were dissected out at P21 for rd1 and P90 for Rho-/-. 1,000 H2BGFP labeled cones per retina sample were FACS sorted out, and subject for RNA-sequencing. Results: >1,400 genes in P21 rd1 and >700 genes in Rho-/- were found differentially expressed with Txnip treatment. Conclusions: 25 genes are in common between P21 rd1 and P90 Rho-/- with Txnip treatment. On this list, notably, three mitochondrial Electron Transport Chain (ETC) genes were up-regulated.

2021-01-20 | GSE161622 | GEO

HDAC inhibition ameliorates cone survival in retinitis pigmentosa mice

Project description:Cone photoreceptor cell death in inherited retinal diseases, such as Retinitis Pigmentosa (RP), leads to the loss of accurate and color vision and ultimately blindness. In RP, a vast number of mutations are affecting the structure and function of rod photoreceptors while cones remain mutation-free. Once majority of rods have degenerated cones are dying secondarily due to the increased oxidative stress, inflammation and loss of structural and nutritional support normally provided by rods. Here we demonstrated that secondary cone cell death in animal models for RP is governed by an increased activity of histone deacetylates (HDACs). A single intravitreal injection of an HDAC inhibitor at a late stage of the disease, when majority of rods have already degenerated, is sufficient to delay cone death and support long-term cone survival. Surviving cones are retaining functionality and are mediating light-driven ganglion cell responses. RNA-seq analysis of surviving cones demonstrated that HDAC inhibition affords multi-level protection trough regulation of different prosurvival pathways including MAPK, PI3K-AKT and autophagy. These study suggest a unique possibility for targeted pharmacological protection of both primary degenerating rods and mutation-free secondary dying cones and creates hope to maintain vision in RP patients independent of the disease stage.

2020-11-04 | GSE141601 | GEO

Rod-derived Cone Viability Factor 2

Project description:Rod-derived Cone Viability Factor (RdCVF) is a truncated thioredoxin secreted by rod photoreceptors that protects cones. Because the secondary loss of cones in retinitis pigmentosa (RP) is the major visual handicap of this untreatable neurodegenerative disease, the administration of RdCVF is thought to be a promising therapy for RP. We show that RdCVF is acting by binding to Basigin-1 (BSG1) at the surface of cones. BSG1 is an alternative splice product of the BSG gene, a transmembrane protein with an extra immunoglobin domain expressed specifically in the retina. BSG1 binds to the glucose transporter GLUT1. RdCVF increases glucose entry into cones. We found that the increase in glucose is used by cones to induce cell survival by stimulating aerobic glycolysis. A disease associated missense mutation of RdCVF results in its inability to bind to BSG1, to stimulate glucose uptake and to prevent secondary cone death of a model of RP.

2016-06-15 | PXD001715 | Pride

Molecular Mechanisms Limiting the Therapeutic Window of AAV Gene Therapy in Mouse Models of Blue Cone Monochromacy

Project description:Blue cone monochromacy (BCM) is an X-linked retinal disorder caused by mutations in the OPN1LW/OPN1MW gene locus, resulting in impaired cone function and structural degeneration. We conducted a comparative analysis of AAV-mediated gene therapy in Opn1lw/Opn1mw double knockout (DKO) and Opn1mwC198R/Opn1sw-/- (C198R) BCM mouse models and evaluated the therapeutic window, efficacy, and longevity. Our results demonstrate that the AAV8-Y733F capsid achieved superior cone rescue compared to AAV5. While both DKO and C198R models showed similar therapeutic windows and rescue longevity, treatment efficacy decreased markedly in older mutant mice. Structural analysis revealed that aged cones in both models displayed degenerative changes, including mislocalized mitochondria and compromised connecting cilia. At the molecular level, we observed reduced AAV-mediated transgene expression in DKO and C198R older cones, which may result from decreased transduction efficiency, decreased circular episome stability, genome-wide transcription/translation downregulation, targeted mRNA/protein degradation, or overall cone degeneration. Notably, the cone-specific promoters for Pde6c and Cngb3 maintained robust activity in degenerating cones. These findings suggest that combining an efficient AAV serotype with an optimized cone promoter could be a viable approach to extend the therapeutic window and enhance treatment longevity for BCM patients.

2025-03-11 | GSE289547 | GEO

Reactivating the phototransduction cascade with a mutation agnostic gene therapy preserves vision in Rod-Cone Dystrophies

Project description:Rod-cone dystrophy (RCD), or retinitis pigmentosa, involves genetic conditions where rod degeneration precedes cone degeneration, resulting in tunnel vision and eventual blindness. Previous studies attempted to restore cone activity and prolong vision by expressing microbial chloride pumps in degenerating cone photoreceptors. However, microbial opsins require high expression and intense light, limiting their effectiveness. In this work, we explored the phototransduction cascade in degenerating cones in two RCD mouse models. We observed that opsin and arrestin expression persists in the soma during outer segment degeneration. This led us to hypothesize that reactivating cones based on cone opsin signaling may be possible by expressing a target channel activated by G proteins recruited by cone opsin. Through adeno-associated viral (AAV) mediated expression of the G protein-coupled inwardly rectifying K (GIRK) channel, we achieved improvements in visual function in two RCD mouse models with mutations in different genes. Importantly, we validated the rationale of GIRK-mediated gene therapy in humans by confirming cone opsin and cone arrestin expression in cones of late-stage RCD patients. Our proposed approach involves GIRK channel expression in cones as a novel method to maintain high acuity, sensitivity, and color vision in RCD, independent of the underlying mutation.

2025-01-13 | GSE286529 | GEO

Single-cell RNA sequencing of the retina in a model of retinitis pigmentosa reveals early responses to degeneration in rods and cones

Project description:In inherited retinal disorders such as retinitis pigmentosa (RP), rod photoreceptor-specific mutations cause primary rod degeneration that is followed by secondary cone death and loss of high-acuity vision. Mechanistic studies of retinal degeneration are challenging because of retinal heterogeneity. Moreover, the detection of early cone responses to rod death is especially difficult due to the paucity of cones in the retina. To resolve heterogeneity in the degenerating retina and investigate events in both types of photoreceptors during primary rod degeneration, we utilized droplet-based single-cell RNA sequencing in an RP mouse model, rd10.

2022-04-13 | GSE183206 | GEO

Growth cone-enriched proteome of embryonic to early postnatal mouse brain

Project description:A growth cone (GC) is a part of a neuron considered a hub for axon growth, motility and guidance functions. Here, we present a dataset on the protein profiling of the growth cone-enriched fractions derived from E18, P0, P3, P6 and P9 C57BL/6J mouse pups. For comparison, we analyzed non-growth cone membranes.

2019-05-03 | PXD012134 | Pride

Retinitis pigmentosa (RP) mouse cone transcriptom change with Txnip treatment

Project description:Retinitis pigmentosa (RP) mouse cone transcriptom change with Txnip treatment

| PRJNA678960 | ENA

Expression data from mouse intestine: C57Bl/6 MTHFR+/- vs BALB/c MTHFR+/-

Project description:Previous studies in our laboratory have shown that low folate diet (control diet with 2mg folate/kg, low folate diet with 0.3mg folate/kg) can induce intestinal tumors in BALB/c mice. In addition, we reported that C57Bl/6J mice did not form tumors under the same conditions. We used microarrays to identify the genetic differences between BALB/c and C57Bl/6J mice that promote tumorigenesis in BALB/c mice.

2013-04-09 | GSE34010 | GEO

Samd7 preserves cell identity and enforces the ‘one neuron-one receptor’ rule in vertebrate photoreceptors [5dpf_td]

Project description:The exclusive expression of single sensory receptors in individual neurons (the ‘one-neuron-one receptor’ rule) is essential for vision and other sensory systems. Here, we show that the transcriptional corepressor Samd7 enforces this rule in vertebrate red cones and acts in other photoreceptor types to maintain cell identity. In the zebrafish samd7-/- retina, red cones are transformed to hybrid red/UV-sensitive cones, green cones are transfated to blue cones, and the number of rods is greatly reduced. In the mouse Samd7-/- retina, dorsal M-cones are transformed to hybrid M/S-cones—analogous to the transformation of red to red/UV cones that occurs in zebrafish—and rods aberrantly express cone genes including S-opsin. Altogether, Samd7 acts to repress short-wavelength cone gene expression in long-wavelength-sensitive cones, thereby sustaining the mutually exclusive patterns of opsin expression and cone identity required for color vision.

2024-06-21 | GSE249755 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data