June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Altered DNA damage and stress pathways in antagomir-treated rodent spaceflight analogs
Author Affiliations & Notes
  • Nicole Bodi
    Pharmacology and Toxicology, Indiana University Purdue University Indianapolis, Indianapolis, Indiana, United States
  • Ryan Miller
    School of Medicine, Indiana University Purdue University Indianapolis, Indianapolis, Indiana, United States
  • Shahna Shahul Hameed
    Ophthalmology, Indiana University Purdue University Indianapolis, Indianapolis, Indiana, United States
  • Angela Kubik
    Center for Biotechnology & Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York, United States
  • Noah Allen
    Center for Biotechnology & Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York, United States
  • Selin Altinok
    McAllister Heart Institute, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
    Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
  • Leah Oswalt
    McAllister Heart Institute, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
    Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
  • Rebekah Sanchez-Hodge
    McAllister Heart Institute, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
    Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
  • Jonathan Schisler
    McAllister Heart Institute, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
    Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
  • Elizabeth Blaber
    Center for Biotechnology & Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York, United States
  • Afshin Beheshti
    Space Biosciences, NASA Ames Research Center, Moffett Field, California, United States
    Stanley Center for Psychiatric Research, Broad Institute, Cambridge, Massachusetts, United States
  • Tasneem Putliwala Sharma
    Ophthalmology, Indiana University Purdue University Indianapolis, Indianapolis, Indiana, United States
    Pharmacology and Toxicology, Indiana University Purdue University Indianapolis, Indianapolis, Indiana, United States
  • Footnotes
    Commercial Relationships   Nicole Bodi None; Ryan Miller None; Shahna Shahul Hameed None; Angela Kubik None; Noah Allen None; Selin Altinok None; Leah Oswalt None; Rebekah Sanchez-Hodge None; Jonathan Schisler None; Elizabeth Blaber None; Afshin Beheshti None; Tasneem Sharma U.S. Patent Application No. 16/395,610, Code P (Patent)
  • Footnotes
    Support  Translational Research Institute of Space Health through NASA Cooperative Agreement NNX16AO69A (T-0404), unrestricted grant from Research to Prevent Blindness, Inc. to the Indiana University School of Medicine, Department of Ophthalmology.
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 5236. doi:
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      Nicole Bodi, Ryan Miller, Shahna Shahul Hameed, Angela Kubik, Noah Allen, Selin Altinok, Leah Oswalt, Rebekah Sanchez-Hodge, Jonathan Schisler, Elizabeth Blaber, Afshin Beheshti, Tasneem Putliwala Sharma; Altered DNA damage and stress pathways in antagomir-treated rodent spaceflight analogs. Invest. Ophthalmol. Vis. Sci. 2023;64(8):5236.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : During long-duration spaceflight, astronauts are exposed to spaceflight stressors, including cosmic radiation and microgravity. Cosmic radiation present during long-duration missions includes ionizing radiation, galactic cosmic radiation (GCR), and solar particle events (SPE) which can contribute to DNA and mitochondrial damage. The mechanism of DNA and mitochondrial damage and impact of spaceflight associated miRNA in the eye after exposure to spaceflight stressors is undetermined. We investigated the expression of DNA damage repair, mitochondrial, and inflammation genes in rodent ocular and spinal samples exposed to spaceflight stressors and consequently treated with antagomirs (Ag) to spaceflight-associated miRNAs.

Methods : 120 female mice were placed into 6 groups: control, control + Ag, simulated GCRs, GCRs + Ag, simulated SPE, and SPE + Ag. Half of each group were housed with hindlimb unloading (HU) to simulate microgravity. The Ag-treated mice were treated every 3 days with the last treatment 24 hours prior to irradiation. Post-irradiation, mice were euthanized, vertebral column and eye globes were dissected. Total RNA was isolated from spinal and ocular tissue. We used qRT-PCR to determine changes between experimental groups (N=6). We analyzed DNA damage repair genes (T53bp1, Atm, Atr, Rad 50, and Brca1), mitochondrial markers (Cmpk2 and Sod2), and inflammation markers (Tlr4, Il6, and Il-1β).

Results : In eyes and spines, there was a decrease of Brca1 under microgravity conditions which was rescued by Ag treatment. However, under GCR conditions, both Ag treated groups had a decrease in T53bp1 expression. In eyes for the mitochondrial genes, there was a decrease in Sod2 expression in the Ag treated groups under GCR conditions and increased inflammatory markers in the radiation groups, which was reduced with Ag treatment. Antagomir treatment increased expression of Atm and T53bp1 in spinal tissue.

Conclusions : Our study validates that there is increased DNA and mitochondrial damage in ocular and spinal tissue after exposure to simulated spaceflight conditions. We demonstrate that antagomir treatment in mice exposed to simulated spaceflight has the potential to reduce the effects of spaceflight stressors.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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