RNA-seq of retinal microglia and non-microglial retina cells in WT (Bmal1f/f) and microglial Bmal1-KO (Bmal1-mg/-mg) mice
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PROVIDER: PRJNA1187531 | ENA |
REPOSITORIES: ENA
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Project description:We discovered that Bmal1 knockdown in retinal microglia alters their diurnal clock gene expression, inflammatory gene expression, and morphology. Furthermore, we found that this disruption of diurnal physiology in microglia results in reduced scotopic visual function, retinal neurodegeneration, and abnormal wheel running behavior in mice, suggesting that maintenance of the microglial clock contributes to retinal homeostasis. Subsequently, we investigated transcriptional alterations in retinal microglia and non-microglial cells in the retina to uncover gene expression patterns that may explain these clock-dependent phenotypes and potentially identify homeostatic neuro-glial signaling mechanisms dependent on microglial clock biology.
2025-07-28 | GSE282175 | GEO
Project description:The study was aimed at comparing the transcriptome of MG cells of the retina with the progenitors derived from them after an injury. This information will help in the identification of factors that are responsible for the retinal regeneration.
2012-08-10 | GSE36191 | GEO
Project description:The study was aimed at comparing the transcriptome of MG cells of the retina with the progenitors derived from them after an injury. This information will help in the identification of factors that are responsible for the retinal regeneration. Muller glia were isolated by fluorescent activated cell sorting (FACS) using uninjured retinas from transgenice zebrafish (gfap:gfp) where green florescent protein (GFP) is under the control of the glial fibrillary acidic protein (gfap) promoter. MG-derived retinal progenitors were isolated by FACS at 4 days post retinal injury from 1016 tuba1a:gfp transgenic fish where GFP is driven by the tuba1a promoter which is specifically activated in these progenitors. Total RNA was isolated from these cell populations and subjected to microarray analysis to compare their transcriptomes. Samples were prepared in duplicate.
2012-08-09 | E-GEOD-36191 | biostudies-arrayexpress
Project description:Emerging evidence suggests a link between the circadian clock and retinopathies though the causality has not been established. Circadian clocks in the mammalian retina regulate a diverse range of retinal functions that allow the retina to adapt to the light-dark cycle. We report that clock genes are expressed in the embryonic retina, and the embryonic retina requires light cues to maintain robust circadian expression of the core clock gene, Bmal1. Deletion of Bmal1 and Per2 from the retinal neurons results in retinal angiogenic defects similar to when animals are maintained under constant light conditions. Using two different models to assess pathological neovascularization, we show that neuronal Bmal1 deletion reduces neovascularization with reduced vascular leakage, suggesting that a dysregulated circadian clock primarily drives neovascularization. Chromatin immunoprecipitation sequencing analysis suggests that semaphorin signaling is the dominant pathway regulated by Bmal1. Our data indicate that therapeutic silencing of the retinal clock could be a common approach for the treatment of certain retinopathies like diabetic retinopathy and retinopathy of prematurity.
2022-07-01 | GSE207271 | GEO
Project description:To investigate the interaction between aging and microglial circadian rhythmicity, we examined mice deficient in the core clock transcription factor, BMAL1, in microglia.
2023-03-01 | GSE214514 | GEO
Project description:To study the development of human retina, we used single cell RNAseq at key fetal stages and followed the development of the major cell types, as well as populations of transitional cells. We also analyzed stem cell (hPSC)-derived retinal organoids; although organoids have a very similar cellular composition at equivalent ages to the fetal retina, there are some differences in gene expression of particular cell types. Moreover, the inner retinal lamination is disrupted in more advanced stages of organoids when compared with fetal retina. To determine whether the disorganization in the inner retina was due to the culture conditions, we analyzed retinal development in fetal retina maintained under similar conditions. These retinospheres develop for at least 6 months, displaying better inner retinal lamination than retinal organoids. Our scRNAseq comparisons between fetal retina, retinal organoids and retinospheres provide a new resource for developing better in vitro models for retinal disease.
2020-01-10 | GSE142526 | GEO
Project description:To understand RS1 gene interaction networks in the X-linked retinoschisis (XLRS) mouse retina (Rs1-/y), we analyzed the transcriptome by RNA sequencing before and after in vivo expression of exogenous retinoschisin (RS1) gene delivered by AAV8. RS1 is a secreted cell adhesion protein that is critical for maintaining structural lamination and synaptic integrity of the neural retina. RS1 loss-of-function mutations cause XLRS disease in young boys and men, with splitting ("schisis") of retinal layers and synaptic dysfunction that cause progressive vision loss with age. Analysis of differential gene expression profiles and pathway enrichment analysis of Rs1-KO (Rs1-/y) retina identified cell surface receptor signaling and positive regulation of cell adhesion as potential RS1 gene interaction networks. Most importantly, it also showed massive dysregulation of immune response genes at early age, with characteristics of a microglia-driven proinflammatory state. Delivery of AAV8-RS1 primed the Rs1-KO retina toward structural and functional recovery. The disease transcriptome transitioned toward a recovery phase with upregulation of genes implicated in wound healing, anatomical structure (camera type eye) development, metabolic pathways, and collagen IV networks that provide mechanical stability to basement membrane. AAV8-RS1 expression also attenuated the microglia gene signatures to low levels toward immune quiescence. This study is among the first to identify RS1 gene interaction networks that underlie retinal structural and functional recovery after RS1 gene therapy. Significantly, it also shows that providing wild-type RS1 gene function caused the retina immune status to transition from a degenerative inflammatory phenotype toward immune quiescence, even though the transgene is not directly linked to microglia function. This study indicates that inhibition of microglial proinflammatory responses is an integral part of therapeutic rescue in XLRS gene therapy, and gene therapy might realize its full potential if delivered before microglia activation and photoreceptor cell death.
2021-06-22 | GSE153874 | GEO
Project description:Microglial gene expression in Bmal1 cKO and WT mice
| PRJNA885784 | ENA
Project description:Objective: Retinal angiomatous proliferation (RAP) represents a special form of neovascular age-related macular degeneration. Immune cells accumulate at RAP, but so far it is unclear whether these cells are resident retinal microglial cells (MG) or blood infiltrating monocytes (MO) and whether these cells can influence RAP formation. The aim of this study is to determine the relative contribution of MG and MO to RAP and to define the transcriptional profile of the dominant cell population. Methods: Vldlr -/- Knockout mice were crossed with MG-specific Cx3cr1CreER/+:Rosa26-Tomfl/+ re-porter mice (MG-Tom). The resulting Vldlr-/-:MG-Tom mice received tamoxifen injection at day 1 after birth (P1), leading to expression of Tomato fluorochrome (Tom) in myeloid cells. Myeloid cells were examined at P17, P31, and P42 by immunohistochemical Iba1 staining and retinal Tom expression. In addition, Tom-positive MG were isolated at P17 by fluorescence-activated cell sorting, and the transcriptional profile of MG was analyzed by RNA sequencing. MG Tom mice, also injected at P1 with tamoxifen, served as controls for RNA-Seq. Results: Our data show that at the beginning of RAP formation (P17), hardly any MO migrates from blood into tissues (0.2±0.5 MO/RAP, 2.0±0.8 MG/RAP). During the course of RAP formation, this changes only slightly (P31: 0.6±2.2 MO/RAP, 10.3±12.8 MG/RAP; P42: 0.6±2.4 MO/RAP, 14.3±9.4 MG/RAP). RNA sequencing of the isolated MG identified 140 differentially expressed genes (DEG), of which 67 were upregulated and 73 were downregulated upon RAP formation. Gene ontology enrichment analysis of the 140 DEGs revealed that they contribute primarily to immune-associated processes, such as leukocyte migration and chemotaxis, regulation of the immune system and immune response, and wound responses. Retinal MG thereby express the pro-angiogenic soluble factor Spp1 (log2FC 1.8) in addition to Ccl2 and Cxcl14 during RAP formation. Conclusion: Our data indicate that resident MG represent the dominant immune cell population during retinal angiomatous proliferation in the Vldlr knockout mouse. RNA sequencing of MG reveals upregulation of immune-associated processes and of pro-angiogenic factors, such as Spp1. Cell-specific modulation of MG may thus form the basis of a future therapeutic option for the treatment of RAP.
2022-06-30 | GSE163642 | GEO
Project description:Purpose: Investigate the molecular determinants of retinal regeneration in adult vertebrates by analyzing the gene expression profiles of control and post-lesion retina of adult zebrafish, a system that regenerates following injury. Methods: Gene expression profiles of zebrafish retina and brain were determined with DNA microarray, RT-PCR, and real-time quantitative PCR analyses. Damaged retinas and their corresponding controls were analyzed 2-5 days post-lesion (acute injury condition) or 14 d post-lesion (cell regeneration condition). Results: Expected similarities and differences in the gene expression profile of zebrafish retina and brain were observed, confirming the applicability of the gene expression techniques. Mechanical lesion of retina triggered significant, time-dependent changes in retinal gene expression. The induced transcriptional changes were consistent with cellular phenomena known to occur, in a time-dependent manner, subsequent to retinal lesion, including cell cycle progression, axonal regeneration, and regenerative cytogenesis. Conclusions: The results indicate that retinal regeneration in adult zebrafish involves a complex set of induced, targeted changes in gene transcription, and suggest that these molecular changes underlie the ability of the adult vertebrate retina to regenerate. Keywords: time course; injury response; cellular correlation Control brain and retina (unlesioned); Control and lesioned retina (matched animals, at least n = 8 for each condition).
2005-09-16 | E-GEOD-3303 | biostudies-arrayexpress