Transcriptome comparison of RhoP23H/+ mouse retina with wildtype at different age
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE281959 | GEO | 2024/12/01
REPOSITORIES: GEO
Similar Datasets
Project description:Transcriptomic profiling in juvenile P23H Retinitis Pigmentosa mouse retinas
| PRJNA639510 | ENA
Project description:Retinal degeneration is the leading cause of irreversible blindness. Retinitis pigmentosa (RP) is a genetically heterogenous group of diseases. In the United States, approximately one in 4000 individuals is affected. RP begins with the loss of night vision due to the loss of rod photoreceptor cells. The disease progresses slowly with the loss of peripheral vision, and eventually leads to complete debilitating and irreversible blindness. The first mutation associated with human RP was identified in the gene encoding rhodopsin, the G-protein coupled receptor of rod photoreceptor cells. Mutations within the rhodopsin gene account for significant portion of RP cases. Specifically, mutations of the proline at residue 347 in rhodopsin have been linked to human RP. We are fortunate to have access to the P347S rhodopsin mutant mice. These mice represent an excellent transgenic mouse model of retinal degeneration. The P347S rhodopsin mutation is one of the best studied mutations, yet the mechanism by which the mutation causes degeneration is still unknown. One study has demonstrated that galectin-1 plays a role in degeneration of neuronal processes (1) and another study has shown that expression level of galectin-3 is elevated in retinas of patients with age-related macular degeneration. These studies in conjunction with the availibility of the P347S mutant mice have provided impetus to examine the pathogenesis of retinal degeneration in the context of the possible role of glycans and glycan-binding proteins. The time course of photoreceptor degeneration in the P347S mouse model has been carefully studied. In these mice, degeneration is barely detectable at 1 month of age, yet biochemical evidence suggests that the rod photoreceptor cells have already begun to die. At 4 months of age, approximately half of the rod photoreceptor cells have degenerated. To distinguish involvement of glycogens at the various stages of retinal degeneration, we have collected retinas of wild type and the mutant mice at four time points (1, 2, 3, and 4 months of age). This will allow us to identify the genes that target early, mid- and late stages of the retinal degeneration process. Thus we request the analysis of total 24 samples as specified below: Age Group (months) Mice No of samples at each time point 1 Wild type 3 2 Wild type 3 3 Wild type 3 4 Wild type 3 1 P347S 3 2 P347S 3 3 P347S 3 4 P347S 3 Total 24.
2011-09-07 | E-GEOD-31990 | biostudies-arrayexpress
Project description:Expression of miRNA analysis in mouse retinocytes was analysed using Next-generation sequencing (NGS) method in Rhodopsin DNA Nanoparticles treated P23H Knock-in Heterozygous Mouse (P23H+/-).
2020-06-24 | GSE153053 | GEO
Project description:Neuronal plasticity of the inner retina has been observed in response to photoreceptor degeneration. Typically, this phenomenon has been considered maladaptive and may preclude vision restoration in the blind. However, several recent studies utilizing triggered photoreceptor ablation have shown adaptive responses in bipolar cell dendrites expected to support normal vision. Whether such homeostatic plasticity occurs during progressive photoreceptor degenerative disease to help maintain normal visual behavior is unknown. We addressed these issues in an established mouse model of Retinitis Pigmentosa caused by the P23H mutation in rhodopsin. We show robust modulation of the retinal transcriptomic network reminiscent of the neurodevelopmental state as well as potentiation of rod – rod bipolar cell signaling following rod photoreceptor degeneration. Additionally, we found highly sensitive night vision in P23H mice even when more than half of the rod photoreceptors were lost. The results implicate retinal adaptation leading to persistent visual function during photoreceptor degenerative disease.
2020-08-21 | GSE156533 | GEO
Project description:Neuronal plasticity of the inner retina has been observed in response to photoreceptor degeneration. Typically, this phenomenon has been considered maladaptive and may preclude vision restoration in the blind. However, several recent studies utilizing triggered photoreceptor ablation have shown adaptive responses in bipolar cell dendrites expected to support normal vision. Whether such homeostatic plasticity occurs during progressive photoreceptor degenerative disease to help maintain normal visual behavior is unknown. We addressed these issues in an established mouse model of Retinitis Pigmentosa caused by the P23H mutation in rhodopsin. We show robust modulation of the retinal transcriptomic network reminiscent of the neurodevelopmental state as well as potentiation of rod – rod bipolar cell signaling following rod photoreceptor degeneration. Additionally, we found highly sensitive night vision in P23H mice even when more than half of the rod photoreceptors were lost. The results implicate retinal adaptation leading to persistent visual function during photoreceptor degenerative disease.
2020-06-16 | GSE152474 | GEO
Project description:Transcriptomic profiling in 3-month-old P23H Retinitis Pigmentosa mouse retinas
| PRJNA658272 | ENA
Project description:P23H is the most common mutation in the RHODOPSIN (RHO) gene leading to a dominant form of retinitis pigmentosa (RP), a rod photoreceptor degeneration that invariably causes vision loss. Specific disruption of the disease P23H RHO mutant while preserving the wild-type (WT) functional allele would be an invaluable therapy for this disease. However, various technologies tested in the past failed to achieve effective changes and consequently therapeutic benefits. We validated a CRISPR/Cas9 strategy to specifically inactivate the P23H RHO mutant, while preserving the WT allele in vitro. We, then, translated this approach in vivo by delivering the CRISPR/Cas9 components in murine Rho+/P23H mutant retinae. Targeted retinae presented a high rate of cleavage in the P23H but not WT Rho allele. This gene manipulation was sufficient to slow photoreceptor degeneration and improve retinal functions. To improve the translational potential of our approach, we tested intravitreal delivery of this system by means of adeno-associated viruses (AAVs). To this purpose, the employment of the AAV9-PHP.B resulted the most effective in disrupting the P23H Rho mutant. Finally, this approach was translated successfully in human cells engineered with the homozygous P23H RHO gene mutation. Overall, this is a significant proof-of-concept that gene allele specific targeting by CRISPR/Cas9 technology is specific and efficient and represents an unprecedented tool for treating RP and more broadly dominant genetic human disorders affecting the eye, as well as other tissues.
2019-03-20 | GSE128579 | GEO
Project description:Rhodopsin is essential for phototransduction, and many rhodopsin mutations cause heritable retinal degenerations. The P23H rhodopsin variant generates a misfolded rhodopsin protein that photoreceptors quickly target for degradation by mechanisms that are incompletely understood. To gain insight into how P23H rhodopsin is removed from rods, we used mass spectrometry to identify protein interaction partners of P23H rhodopsin immunopurified from RhoP23H/P23H mice and to compare with protein interaction partners of wild-type rhodopsin from Rho+/+ mice. We identified 286 proteins associated with P23H rhodopsin and 276 proteins associated with wild-type rhodopsin. Only 113 proteins were shared between wild-type and mutant rhodopsin protein interactomes. In the P23H rhodopsin protein interactome, we saw loss of phototransduction, retinal cycle, and rhodopsin protein trafficking proteins but gain of ubiquitin-related proteins when compared with the wild-type rhodopsin protein interactome. In the P23H rhodopsin protein interactome, we saw significant enrichment of gene ontology terms related to ER-associated protein degradation, ER stress, and translation. Protein-protein interaction network analysis revealed that translational and ribosomal quality control proteins were the most significant regulators in the P23H rhodopsin protein interactome. The protein partners identified in our study may provide new insights into how photoreceptors recognize and clear mutant rhodopsin and may offer novel targets involved in retinal degeneration pathogenesis.
2022-08-24 | MSV000090197 | MassIVE
Project description:Purpose: The goals of this study is to analyze the transcriptome change during retinal explant culture treated with pharmacological chaperone of rhodopsin (YC-001). Methods: The WT and RhoP23H/+ mouse eyes were enucleated at post natal day 15 and retinal explant were cultured for 24 hours followed by the 24 hours treatment with pharmacological chaperone of rhodopsin (YC-001) and dmso vehicle control. Another group of P23H/+ retinal explant was treated further till 9 days. We compare the transcript of RhoP23H/+ dmso with WT dmso at 24 hour treatment (1 days in vitro (1DIV)). RhoP23H/+ YC-001 were also compared with RhoP23H/+ dmso treated retinal explant at 1DIV and 9DIV. Results: A total of 338 differentially expressed genes (DEGs) were identified comparing the RhoP23H/+ vs. WT retinal explants with DMSO and 56 DEGs were identified comparing RhoP23H/+ YC-001 treated vs. DMSO treated retinal explant at 1 DIV. Further we observed an increased number of DEGs (8,597) comparing RhoP23H/+ vs dmso vehicle control at 9DIV. DEGs were identified using stringency with >1.5-fold change and P-value<0.05. Interestingly, we found 40 common genes when comparing RhoP23H/+ YC-001 treated vs. DMSO at 1DIV and 9DIV. Conclusions: This study used RNA-seq technology which represents the transcriptome of WT and RhoP23H/+ mouse retinal explant with and without pharmacological chaperone of rhodopsin (YC-001). Our NGS results show that YC-001 affect many biological pathways including visual transduction, protein homeostasis pathways and decreases the expression of immune response activation genes, to rescue the rhodospin homeostasis and retinal morphology in the retinal explant of P23H Rho mouse model of retinitis pigmentosa (RP).
2021-07-10 | GSE179754 | GEO
Project description:A hallmark of inherited retinal degenerative diseases such as Retinitis Pigmentosa (RP) is progressive structural and functional remodeling of the remaining retinal cells as photoreceptors degenerate. Extensive remodeling of the retina stands as a barrier for the successful implementation of strategies to restore vision. To understand the molecular basis of remodeling, we performed analyses of single-cell transcriptome data from adult Zebrafish retina of wild-type and a P23H mutant rhodopsin transgenic model of RP with continuous degeneration and regeneration. We provide a benchmark atlas of retinal cell type transcriptomes in Zebrafish and find changes in all retinal cell types in the P23H model. These include widespread oxidative stress, changes in reliance on oxidative metabolism and glycolysis, widespread synaptic remodeling, and changes in circadian rhythm regulation. This comprehensive transcriptomic analysis provides a molecular road map to understand how the retina remodels in the context of chronic retinal degeneration with ongoing regeneration.
2023-11-10 | GSE234435 | GEO