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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE131954 | GEO | 2019/05/31

REPOSITORIES: GEO

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Project description:Proper spatial differentiation of retinal cell types is necessary for normal human vision. Many retinal diseases, such as Best disease and male germ cell associated kinase (MAK)-associated retinitis pigmentosa, preferentially affect distinct topographic regions of the retina. While much is known about the distribution of cell types in the retina, the distribution of molecular components across the posterior pole of the eye has not been well-studied. To investigate regional difference in molecular composition of ocular tissues, we assessed differential gene expression across the temporal, macular, and nasal retina and retinal pigment epithelium (RPE)/choroid of human eyes using RNA-Seq. RNA from temporal, macular, and nasal retina and RPE/choroid from four human donor eyes was extracted, poly-A selected, fragmented, and sequenced as 100 bp read pairs. Digital read files were mapped to the human genome and analyzed for differential expression using the Tuxedo software suite. Retina and RPE/choroid samples were clearly distinguishable at the transcriptome level. Numerous transcription factors were differentially expressed between regions of the retina and RPE/choroid. Photoreceptor-specific genes were enriched in the peripheral samples, while ganglion cell and amacrine cell genes were enriched in the macula. Within the RPE/choroid, RPE-specific genes were upregulated at the periphery while endothelium associated genes were upregulated in the macula. Consistent with previous studies, BEST1 expression was lower in macular than extramacular regions. The MAK gene was expressed at lower levels in macula than in extramacular regions, but did not exhibit a significant difference between nasal and temporal retina. The regional molecular distinction is greatest between macula and periphery and decreases between different peripheral regions within a tissue. Datasets such as these can be used to prioritize candidate genes for possible involvement in retinal diseases with regional phenotypes. Reprinted from <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=25446321">Whitmore, S.S., Wagner, A.H., DeLuca, A.P., Drack, A.V., Stone, E.M., Tucker, B.A., Zeng, S., Braun, T.A., Mullins, R.F., Scheetz, T.E., 2014. Transcriptomic analysis across nasal, temporal, and macular regions of human neural retina and RPE/choroid by RNA-Seq. Experimental Eye Research</a>. Used under <a href="http://creativecommons.org/licenses/by-nc-sa/3.0/">Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported </a>license. Additional RNA sequencing was performed on temporal, macular, nasal, inferior, and superior retina from a fifth subject and is included in this dataset. See original publication for details.

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

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