Dataset Information

Spaceflight influences gene expression, photoreceptor integrity, and oxidative stress-related damage in the murine retina.

ABSTRACT: 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.

SUBMITTER: Overbey EG

PROVIDER: S-EPMC6746706 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Spaceflight influences gene expression, photoreceptor integrity, and oxidative stress-related damage in the murine retina.

Overbey Eliah G EG da Silveira Willian Abraham WA Stanbouly Seta S Nishiyama Nina C NC Roque-Torres Gina D GD Pecaut Michael J MJ Zawieja David Carl DC Wang Charles C Willey Jeffrey S JS Delp Michael D MD Hardiman Gary G Mao Xiao Wen XW

Scientific reports 20190916 1

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. ...[more]

PMID: 31527661

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Project description:The peroxisome proliferator-activated receptor ? coactivator 1 (PGC-1) proteins are key regulators of cellular bioenergetics and are accordingly expressed in tissues with a high energetic demand. For example, PGC-1? and PGC-1? control organ function of brown adipose tissue, heart, brain, liver and skeletal muscle. Surprisingly, despite their prominent role in the control of mitochondrial biogenesis and oxidative metabolism, expression and function of the PGC-1 coactivators in the retina, an organ with one of the highest energy demands per tissue weight, are completely unknown. Moreover, the molecular mechanisms that coordinate energy production with repair processes in the damaged retina remain enigmatic. In the present study, we thus investigated the expression and function of the PGC-1 coactivators in the healthy and the damaged retina. We show that PGC-1? and PGC-1? are found at high levels in different structures of the mouse retina, most prominently in the photoreceptors. Furthermore, PGC-1? knockout mice suffer from a striking deterioration in retinal morphology and function upon detrimental light exposure. Gene expression studies revealed dysregulation of all major pathways involved in retinal damage and apoptosis, repair and renewal in the PGC-1? knockouts. The light-induced increase in apoptosis in vivo in the absence of PGC-1? was substantiated in vitro, where overexpression of PGC-1? evoked strong anti-apoptotic effects. Finally, we found that retinal levels of PGC-1 expression are reduced in different mouse models for retinitis pigmentosa. We demonstrate that PGC-1? is a central coordinator of energy production and, importantly, all of the major processes involved in retinal damage and subsequent repair. Together with the observed dysregulation of PGC-1? and PGC-1? in retinitis pigmentosa mouse models, these findings thus imply that PGC-1? might be an attractive target for therapeutic approaches aimed at retinal degeneration diseases.

Dataset Information

Spaceflight influences gene expression, photoreceptor integrity, and oxidative stress-related damage in the murine retina.

Publications

Spaceflight influences gene expression, photoreceptor integrity, and oxidative stress-related damage in the murine retina.

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