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Multi-Omics Study of the Effect of Redox-Active Metalloporphyrin on Murine Retina During SpaceflightAstronauts returning from spaceflight have experienced eye problems, which may decrease retinal performance and lead to long-term effects on visual acuity. This study leverages the collected data from spaceflown murine retinas that were treated with redox-active metalloporphyrin (BuOE) to mitigate spaceflight-induced changes and respective ground controls. 10-week-old adult C57BL/6 male mice (n=5 in each of BuOE treated and saline control groups for spaceflown and ground control samples) were flown on Space-X 24 to the ISS national lab, kept in low earth orbit for 35 days and returned to Earth alive. Our multi-omics analysis of RNA-sequencing and reduced representation bisulfite sequencing (RRBS) data generated from subsequent murine retina tissues uncovered genes, pathways, and epigenetic modifications consistent with therapeutic potential of BuOE. From RNA-Seq analysis of spaceflown murine samples, the treatment group show differentially expressed genes relative to saline controls that reached significance (adjusted p-value < 0.05) and included genes Gpx3 and Crhbp, which are related to protection against cell oxidative damage and cellular response to organonitrogen compounds. Ranked fold-changes from the same contrast were used for gene set enrichment analysis, which showed biological processes reaching significance (adjusted p-value < 0.05) including glutathione metabolic processes and cellular response to xenobiotic stimulus. RRBS data of the spaceflown murine samples found 139 hyper or hypo differentially methylated sites spread across chromosomes 1-19 (20% promoters, 21% exons, 43% introns | 20 CpG islands, 7 CpG shores) with a 10% methylation difference (q-value < 0.05).The findings from this investigation have the potential to provide valuable insights into the molecular mechanisms underlying conditions like spaceflight associated neuro-ocular syndrome and assess the effectiveness of BuOE as a countermeasure for astronauts experiencing neuro-ophthalmic abnormalities, which can lead to long-term effects on visual acuity.
Document ID
20240001447
Acquisition Source
Johnson Space Center
Document Type
Presentation
Authors
Hari Ilangovan
(Science Applications International Corporation (United States) McLean, Virginia, United States)
Katherine Hoadley ORCID
(KBR (United States) Houston, Texas, United States)
S Robin Elgart ORCID
(University of Houston Houston, Texas, United States)
Greg Eley
(KBR (United States) Houston, Texas, United States)
Parastou Eslami ORCID
(KBR (United States) Houston, Texas, United States)
Xiao Wen (Vivien) Mao ORCID
(Loma Linda University Loma Linda, California, United States)
Janapriya Saha
(KBR (United States) Houston, Texas, United States)
Date Acquired
January 31, 2024
Publication Date
February 13, 2024
Publication Information
Publisher: National Aeronautics and Space Administration
Subject Category
Life Sciences (General)
Meeting Information
Meeting: Human Research Program-Investigators Working Group (HRP-IWG) Workshop
Location: Galveston, TX
Country: US
Start Date: February 13, 2024
End Date: February 16, 2024
Sponsors: National Aeronautics and Space Administration
Funding Number(s)
WBS: 651549.01.04.10
CONTRACT_GRANT: NNX16MB01C
CONTRACT_GRANT: NNJ15HK11B
Distribution Limits
Public
Copyright
Portions of document may include copyright protected material.
Technical Review
Single Expert
Keywords
Biostatistics
Genomics
RNA-Sequencing
Transcriptomics
Spaceflight
DNA Methylation
RRBS
Space Radiation
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