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Nrf2 overexpression rescues RPE morphology in mouse models of retinitis pigmentosa [rd1-p20_p40_analysis]

ABSTRACT: Contribution of Nrf2 overexpression to the rescue of the RPE and/or photoreceptors in the PDEb (rd1 and rd10) model of retinal degeneration

ORGANISM(S): Mus musculus

PROVIDER: GSE161102 | GEO | 2021/04/28

REPOSITORIES: GEO

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Nrf2 overexpression rescues RPE morphology in mouse models of retinitis pigmentosa [rd1-p20_analysis]

Project description:Contribution of Nrf2 overexpression to the rescue of the RPE and/or photoreceptors in the PDEb (rd1) model of retinal degeneration

2021-04-28 | GSE161103 | GEO

Nrf2 overexpression rescues RPE morphology in mouse models of retinitis pigmentosa [rd1-p40_analysis]

Project description:Contribution of Nrf2 overexpression to the rescue of the RPE and/or photoreceptors in the PDEb (rd1) model of retinal degeneration

2021-04-28 | GSE161104 | GEO

Nrf2 overexpression rescues RPE morphology in mouse models of retinitis pigmentosa [CD1-p40_analysis]

Project description:Contribution of Nrf2 overexpression to the rescue of the RPE and/or photoreceptors in CD1 wild type mice

2021-04-28 | GSE161105 | GEO

Nrf2 overexpression rescues RPE morphology in mouse models of retinitis pigmentosa [rd1-p20_p40_analysis]

Project description:Nrf2 overexpression rescues RPE morphology in mouse models of retinitis pigmentosa [rd1-p20_p40_analysis]

| PRJNA675586 | ENA

Nrf2 overexpression rescues RPE morphology in mouse models of retinitis pigmentosa [rd1-p40_analysis]

Project description:Nrf2 overexpression rescues RPE morphology in mouse models of retinitis pigmentosa [rd1-p40_analysis]

| PRJNA675588 | ENA

Nrf2 overexpression rescues RPE morphology in mouse models of retinitis pigmentosa [rd1-p20_analysis]

Project description:Nrf2 overexpression rescues RPE morphology in mouse models of retinitis pigmentosa [rd1-p20_analysis]

| PRJNA675587 | ENA

Nrf2 overexpression rescues RPE morphology in mouse models of retinitis pigmentosa

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-04-28 | GSE161106 | GEO

Nrf2 overexpression rescues the RPE in mouse models of retinitis pigmentosa.

Project description:Nrf2, a transcription factor that regulates the response to oxidative stress, has been shown to rescue cone photoreceptors and slow vision loss in mouse models of retinal degeneration (rd). The retinal pigment epithelium (RPE) is damaged in these models, but whether it also could be rescued by Nrf2 has not been previously examined. We used an adeno-associated virus (AAV) with an RPE-specific (Best1) promoter to overexpress Nrf2 in the RPE of rd mice. Control rd mice showed disruption of the regular array of the RPE, as well as loss of RPE cells. Cones were lost in circumscribed regions within the cone photoreceptor layer. Overexpression of Nrf2 specifically in the RPE was sufficient to rescue the RPE, as well as the disruptions in the cone photoreceptor layer. Electron microscopy showed compromised apical microvilli in control rd mice but showed preserved microvilli in Best1-Nrf2-treated mice. The rd mice treated with Best1-Nrf2 had slightly better visual acuity. Transcriptome profiling showed that Nrf2 upregulates multiple oxidative defense pathways, reversing declines seen in the glutathione pathway in control rd mice. In summary, Nrf2 overexpression in the RPE preserves RPE morphology and survival in rd mice, and it is a potential therapeutic for diseases involving RPE degeneration, including age-related macular degeneration (AMD).

| S-EPMC7934854 | biostudies-literature

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

Rod photoreceptors degeneration in the rd1 model of retinitis pigmentosa involves a cascade of events leading to proteasome dysfunction

Project description:Retinitis pigmentosa is an inherited disease with sequential retinal degeneration of rod then cone photoreceptors leading to blindness. As in this human syndrome the rd1 mouse model carries a recessive mutation in the rod-specific cGMP phosphodiesterase beta subunit gene leading to rod followed by cone photoreceptor death. The cascade of early events leading to the induction of rod cell death through apoptosis remains unknown. We report a differential whole-genome expression profiling analysis of the wild-type and rd1 mouse retinal transcriptional program using high-density oligonucleotide microarrays with a time series experiment spanning the entire rod photoreceptor degeneration process. Among the 1252 genes found to be significantly differentially expressed, a key group of 19 loci showed distinct differences in expression early in development, suggesting that these genes of clinical interest may play a fundamental role in the induction of the rod photoreceptor degeneration.

2020-09-25 | GSE62020 | GEO

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