Spaceflight causes changes in gene expression, photoreceptor integrity, and oxidative stress-related damage in the murine retina
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ABSTRACT:
PROVIDER: PRJNA545432 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9158520.fastq.gz | Fastqsanger.gz | |||
| SRR9158521.fastq.gz | Fastqsanger.gz | |||
| SRR9158512.fastq.gz | Fastqsanger.gz | |||
| SRR9158522.fastq.gz | Fastqsanger.gz | |||
| SRR9158513.fastq.gz | Fastqsanger.gz |
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Project description:Purpose:The purpose of this study was to determine whether the spaceflight environment induces oxidative damage on ocular structure and how gene expression profiles change during spaceflight. Methods: RNA sequencing, immunofluorescence, and microCT assays were performed on two groups of mice to assess the effects of spaceflight on the mammalian retina. Ten week old adult C57BL/6 mice was flown aboard the ISS for 35 days and returned to Earth alive. Ground control mice were maintained on Earth in identical flight hardware. Within 38 (+/-4) hours of splashdown, mice were euthanized and ocular tissues were collected for analysis. Results:RNA sequencing detected 600 differentially expressed genes in spaceflight retina. This set of differentially expressed genes is enriched for genes related to visual perception, the phototransduction pathway, and numerous retina and photoreceptor phenotype categories. Eleven of the differentially expressed genes are associated with the disease retinitis pigmentosa, a retinal disease characterized by dystrophy of the rods and cones of the photoreceptor layer. Analysis of differentially expressed transcription factors indicate changes in chromatin structure, offering clues to the causes of the phenotypic changes observed. Additionally, immunofluorescence assays showed degradation of cone photoreceptors and increased oxidative stress in the retina. Retinal thickness, as well as thickness of the retinal pigment epithelium and choroid layers, were significantly reduced after spaceflight. Conclusions: These results indicate that retinal performance may decrease over extended periods of spaceflight and cause visual impairment.
2019-05-31 | GSE131954 | GEO
Project description:Extended spaceflight has been shown to adversely affect astronaut visual acuity. The purpose of this study was to determine whether spaceflight alters gene expression profiles and induces oxidative damage in the retina. Ten week old adult C57BL/6 male mice were flown aboard the ISS for 35 days and returned to Earth alive. Ground control mice were maintained on Earth under identical environmental conditions. Within 38 (+/-4) hours after splashdown, mice ocular tissues were collected for analysis. RNA sequencing detected 600 differentially expressed genes (DEGs) in murine spaceflight retinas, which were enriched for genes related to visual perception, the phototransduction pathway, and numerous retina and photoreceptor phenotype categories. Twelve DEGs were associated with retinitis pigmentosa, characterized by dystrophy of the photoreceptor layer rods and cones. Differentially expressed transcription factors indicated changes in chromatin structure, offering clues to the observed phenotypic changes. Immunofluorescence assays showed degradation of cone photoreceptors and increased retinal oxidative stress. Total retinal, retinal pigment epithelium, and choroid layer thickness were significantly lower after spaceflight. These results indicate that retinal performance may decrease over extended periods of spaceflight and cause visual impairment.
| S-EPMC6746706 | biostudies-literature
Project description:This quantitative protepomics study (TMT10 isobaric labeling) of the protein expression in the retina of Msi1/Msi2 double knockout mouse compared to floxed controls. The Msi1 and Msi2 genes were knocked out in photoreceptor cells using tamoxifen inducible Cre (Cre-ERT2) under the control of Pde6g promoter. Tamoxifen was administered by intrapertoneal injection for three consecutive day starting at postnatald day 30, and the retina was collected at postnatal day 51. Retinas from floxed animals lacking the Cre recombinase and treated with tamoxifen were used as controls. Five biological replicates for each knockout (three femailes, two males) and control (two femaes and three males) group were used.
2022-03-10 | PXD030748 | Pride
Project description:Age-related macular degeneration (AMD), a prevalent neurodegenerative disorder, remains the leading cause of vision loss among the elderly population. Despite the urgent need, effective treatments or preventive strategies for AMD are not available. Recent studies have highlighted the potential neuroprotective benefits of intermittent fasting (IF) in several models of aging and age-associated disorders. However, its efficacy in AMD has not been established. Our current research reveals that IF alleviated neurodegeneration by reducing RPE and photoreceptor cell damage in an oxidative stress-induced mouse model of AMD. The assessment of visual capabilities in mice through optomotor response (OMR) tests indicates that IF markedly preserved visual function in NaIO3-treated mice. To understand the mechanism by which IF exerts its protective effects, we performed transcriptome analyses and found that IF can counteract numerous transcriptional alterations induced by NaIO3, predominantly affecting genes involved in photoreceptor structure, inflammatory pathways and reactive oxygen species (ROS) process. Further, we demonstrated through multiple experiments that IF could effectively reduce ROS levels and restraining the hyperactivation of microglia and Müller cells within the RPE and retina. Moreover, we explored the initiation of IF at a later stage in an individual's lifespan and found that benefits were also obtained in the AMD model. Collectively, this study indicates IF exerts neuroprotective effects by reducing ROS production and inflammation in the retina, and is expected to become a new strategy for retinal degenerative diseases caused by oxidative damage, incluiding AMD.
2024-07-09 | GSE271791 | GEO
Project description:Illumina NGS RNA-seq and RRBS Sequencing on Spaceflight Mouse Retina
| PRJNA670470 | ENA
Project description:We reported the retinal transcriptome and methylome profiles of spaceflight and habitat control mice. The retinal transcrtiome was generated including 764 million paired-end 75x2 bp RNA-seq data. The methylome was generated including 788 million 75-bp RRBS DNA methylation data. We identified 177 differentially expressed genes (DEGs) induced by spaceflight based on the RNA-seq dataset, and 643 differentially methylated genes (DMGs) based on RRBS dataset. Functional enrichement analysis based on DEGs and DMGs revealed that spaceflight altered extracellular matrix component (EMC), cell to cell junction, inflammation pathway, wound-healing process, etc. Integration analysis based on transcriptome and methylome suggested that modifications on DNA methylation were correlated with transcriptome changes for several significant biological processes and/or pathways.
2021-06-30 | GSE159771 | GEO
Project description:The rod photoreceptor-specific neural retina leucine zipper protein Nrl is essential for rod differentiation and plays a critical role in regulating gene expression. In the mouse retina, rods account for 97% of the photoreceptors; however, in the absence of Nrl (Nrl-/-), no rods are present and a concomitant increase in cones is observed. Using mouse GeneChips (Affymetrix), we have generated expression profiles of the wild-type and Nrl-/- retina at three time-points representing distinct stages of photoreceptor differentiation. Experiment Overall Design: Both the Nrl-/- mice and wild type controls were of a matched mixed genetic background (R1 and C57BL/6 strains).
2009-10-30 | E-GEOD-8972 | biostudies-arrayexpress
Project description:Due to the high energy demands and characteristic morphology, retinal photoreceptor cells require the specialized lipid metabolism for survival and functions. In this study, we focus on the roles of saturated fatty acids and their metabolism in these processes. Frame-shift mutation of lysophosphatidylcholine acyltransferase 1 (Lpcat1), which introduces saturated fatty acid into lysophosphatidylcholine to produce disaturated phosphatidylcholine (PC), has been reported as a causative for spontaneous retinal degeneration in mice (rd11 mice). However, the molecular basis of retinal degeneration caused by Lpcat1 mutation remains unclear. Here, we report that Lpcat1 deficiency induces light-independent and photoreceptor-specific apoptosis in mice. Lipidomic analyses of retina and isolated photoreceptor outer segment (OS) suggested that loss of Lpcat1 affects not only disaturated PC production, but also the proper cellular fatty acid flux presumably through altering saturated fatty acyl-CoA availabilities. Furthermore, we demonstrated that Lpcat1 deletion increased mitochondrial reactive oxygen species (ROS) levels in photoreceptor cells, but not in other retinal cells, without affecting the OS structure and trafficking of OS localized proteins. These results suggested that LPCAT1-dependent production of disaturated PC is critical for metabolic adaptation during photoreceptor maturation. Our findings highlight the therapeutic potential of saturated fatty acid metabolism in photoreceptor cell degeneration-related retinal diseases.
2022-01-01 | GSE184815 | GEO
Project description:Due to the high energy demands and characteristic morphology, retinal photoreceptor cells require a specialized lipid metabolism for survival and function. This study focused on the roles of saturated fatty acids and their metabolism. A frameshift mutation of lysophosphatidylcholine acyltransferase 1 (Lpcat1), introducing saturated fatty acids into lysophosphatidylcholine to produce disaturated phosphatidylcholine (PC), has been reported to cause spontaneous retinal degeneration in mice (rd11 mice). In this study, we performed a detailed characterization of Lpcat1 in the retina and found that Lpcat1 deficiency induces light-independent and photoreceptor-specific apoptosis in mice. Lipidomic analyses of the retina and isolated photoreceptor outer segment (OS) suggested that loss of Lpcat1 affects disaturated PC production and the proper cellular fatty acid flux, presumably by altering saturated fatty acyl-CoA availabilities. Furthermore, we demonstrated that Lpcat1 deletion increased mitochondrial reactive oxygen species (ROS) levels in photoreceptor cells, but not in other retinal cells without affecting the OS structure and trafficking of OS-localized proteins. These results suggest that the LPCAT1-dependent production of disaturated PC is critical for metabolic adaptation during photoreceptor maturation. Our findings highlight the therapeutic potential of saturated fatty acid metabolism in photoreceptor cell degeneration-related retinal diseases.
2022-01-01 | GSE184817 | GEO
Project description:The rd1 mouse retina is a well-studied model of retinal degeneration where rod photoreceptors undergo cell death beginning at postnatal day P10 until P21. This period coincides with photoreceptor terminal differentiation in a normal retina. We have used the rd1 retina as a model to investigate early molecular defects in developing rod photoreceptors prior to the onset of degeneration. Using a microarray approach, we performed gene profiling comparing rd1 and wild type retinas at four time points starting at P2, prior to any obvious biochemical or morphological differences, and concluding at P8, prior to the initiation of cell death. We have identified genes that are differentially regulated in the rd1 retina at early time points, which may give insights into developmental defects that precede photoreceptor cell death. This is the first report of PRA1 expression in the retina. Our data support the hypothesis that PRA1 plays an important role in vesicular trafficking between the Golgi and cilia in differentiating and mature rod photoreceptors. Retinal samples were harvested from both rd1/le and wt animals at postnatal days 2, 4, 6, and 8 for microarray. Each sample included 8-14 retinas and experiments were performed in quadruplicate. Ten micrograms of total RNA was used for cDNA systhesis in target molecule production.
2012-11-02 | E-GEOD-41821 | biostudies-arrayexpress