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Gene expression changes in the retina following human neural progenitor cell injection into a rodent model for retinal degeneration

ABSTRACT: The goal of this study is to compare gene expression changes in retinal degenerate Royal College of Surgeons (RCS) rats following an injection of human neural progenitor cells (hNPCs) using RNA-seq, as compared to RCS rats receiving a sham surgery and wild-type Long Evans rats. These changes may lead to understanding of the therapeutic potential of hNPCs in inducing photoreceptor survival and visual function preservation.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE70600 | GEO | 2016/05/16

SECONDARY ACCESSION(S): PRJNA289237

REPOSITORIES: GEO

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Gene expression changes in the retina following human neural progenitor cell injection into a rodent model for retinal degeneration

Project description:The goal of this study is to compare gene expression changes in retinal degenerate Royal College of Surgeons (RCS) rats following an injection of human neural progenitor cells (hNPCs) using RNA-seq, as compared to RCS rats receiving a sham surgery and wild-type Long Evans rats. These changes may lead to understanding of the therapeutic potential of hNPCs in inducing photoreceptor survival and visual function preservation. RNA-seq from wild-type Long Evans rats, retinal degenerate Royal College of Surgeons (RCS) rats, and RCS rats following transplantation of human neural progenitor cells (hNPCs)

2016-05-16 | E-GEOD-70600 | biostudies-arrayexpress

Retinal gene expression changes from post-natal 21 (p21) to p60 during retinal degeneration in RCS rat.

Project description:Molecular mechanisms underlying retinal degeneration are not well characterized including in the widely utilized Royal College of Surgeons (RCS) rat model of retinal degeneration. To better understand molecular pathways driving retinal degeneration we performed mRNA transcriptomics on RCS retinas following the natural progression of the disease. This data can identify novel therapeutic targets for future development.

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In vitro and in vivo proteomic comparison of human neural progenitor cell-induced photoreceptor survival

Project description:Retinal degenerative diseases are some of the leading causes of blindness with few treatments. Various cell-based therapies have aimed to slow the progression of vision loss by preserving light-sensing photoreceptor cells. A subretinal injection of human neural progenitor cells (hNPCs) into the Royal College of Surgeons (RCS) rat model of retinal degeneration has aided in photoreceptor survival, though the mechanisms are mainly unknown. Identifying the retinal proteomic changes that occur following hNPC treatment will lead to better understanding of neuroprotection. To mimic the retinal environment following hNPC injection, a co-culture system of retinas and hNPCs was developed. Less cell death occurred in RCS retinal tissue co-cultured with hNPCs than in retinas cultured alone, suggesting that hNPCs provide retinal protection in vitro. Comparison of ex vivo and in vivo retinas identified NRF2-mediated oxidative response signaling as an hNPC-induced pathway. This is the first study to compare proteomic changes following treatment with hNPCs in both an ex vivo and in vivo environment, further allowing the use of ex vivo modeling for mechanisms of retinal preservation. Elucidation of the protein changes in the retina following hNPC treatment may lead to the discovery of mechanisms of photoreceptor survival and its therapeutic for clinical applications.

2018-12-17 | PXD011491 | Pride

Identifying Biomarkers of Heterogeneity and Transplantation Efficacy in Retinal Pigment Epithelial Cells [Bulk RNA-seq]

Project description:Transplantation of retinal pigment epithelial (RPE) cells holds great promise for patients with retinal degenerative diseases such as age-related macular degeneration. In-depth characterization of RPE cell product identity and critical quality attributes are needed to enhance efficacy and safety of replacement therapy strategies. Here we characterized an adult RPE stem cell-derived (RPESC-RPE) cell product using bulk and single cell RNA sequencing (sc-RNA-seq), assessing functional cell integration in vitro into a mature RPE monolayer and in vivo efficacy by vision rescue in the Royal College of Surgeons rats. scRNA-seq revealed several distinct subpopulations in the RPESC-RPE product, some with progenitor markers. We identified RPE clusters expressing genes associated with in vivo efficacy and increased cell integration capability. Gene expression analysis revealed a lncRNA (TREX) as a predictive marker of in vivo efficacy. TREX knockdown decreased cell integration while overexpression increased integration in vitro and improved vision rescue in the RCS rats.

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Identifying biomarkers of heterogeneity and transplantation efficacy in retinal pigment epithelial cells

Project description:Transplantation of retinal pigment epithelial (RPE) cells holds great promise for patients with retinal degenerative diseases, such as age-related macular degeneration. In-depth characterization of RPE cell product identity and critical quality attributes are needed to enhance efficacy and safety of replacement therapy strategies. Here, we characterized an adult RPE stem cell-derived (RPESC-RPE) cell product using bulk and single-cell RNA sequencing (scRNA-seq), assessing functional cell integration in vitro into a mature RPE monolayer and in vivo efficacy by vision rescue in the Royal College of Surgeons rats. scRNA-seq revealed several distinct subpopulations in the RPESC-RPE product, some with progenitor markers. We identified RPE clusters expressing genes associated with in vivo efficacy and increased cell integration capability. Gene expression analysis revealed lncRNA (TREX) as a predictive marker of in vivo efficacy. TREX knockdown decreased cell integration while overexpression increased integration in vitro and improved vision rescue in the RCS rats.

2023-08-14 | GSE211189 | GEO

Identifying Biomarkers of Heterogeneity and Transplantation Efficacy in Retinal Pigment Epithelial Cells [scRNA-seq]

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VEGF orchestration of the p130Cas Interactome

Project description:p130Cas is a polyvalent adapter protein essential for cardiovascular development, and with a key role in cell movement. In order to identify the pathways by which p130Cas exerts its biological functions in endothelial cells we mapped the p130Cas interactome and its dynamic changes in response to VEGF using high-resolution mass spectrometry and reconstruction of protein interaction (PPI) networks with the aid of multiple PPI databases. The work presented here was based on a collaboration between University College London and University College Dublin. Dr Ian Evans (first author) and Prof. Ian Zachary (lab head), can be contacted at: Centre for Cardiovascular Biology and Medicine, Division of Medicine The Rayne Building, University College London, London WC1E 6JJ, United Kingdom. Contact details for University College Dublin collaborators can be found below.

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MicroRNAs in adult rodent liver and response to dioxin

Project description:This SuperSeries is composed of the following subset Series: GSE8467: Micro-RNAs in Adult Rat Liver are Refractory to 19 Hours Dioxin Exposure GSE8468: Micro-RNAs levels in wildtype vs. Ahr-null adult mouse liver constitutively and in response to doxin treatment. GSE8469: Micro-RNAs in Adult Long-Evans (Turku/AB) Rat Liver are Refractory to 96 Hours Dioxin Treatment GSE8470: Micro-RNAs in Adult Rat Liver are Refractory to Dioxin Treatment Keywords: SuperSeries Refer to individual Series

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proteomics profiling of early retina degeneration of RCS rats

Project description:We employed proteomics analysis approach for in-depth retinal protein profiling of dystrophic RCS rats and non-dystrophic congenic controls through LTQ-orbitrap MS. We aim to identify the key molecular pathways and transcript factors involved in early retinal degeneration by differential proteomics analysis.

2017-07-24 | PXD004094 | Pride

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