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The Spaceflight Associated Neuro-ocular Syndrome (SANS) observed in astronauts is hypothesized to be associated with microgravity-induced fluid shifts. Presently, there is a need for an animal model of SANS in order to investigate its pathophysiology. We used the rat hindlimb suspension (HS) model to examine the relationship between the assumed cephalad fluid shifts, intraocular (IOP) pressure, and the molecular responses to the prolonged change in body posture elicited in the retina in order to assess its value as a model of SANS. Young male, young female, and old male Long Evans rats were subjected to HS up to 90 days. Animals completing 90-day suspension were further studied for recovery periods up to 90 additional days at normal posture. IOP measures showed elevated pressure in HS animals for all cohorts with differences in the course of the response between the cohorts. Transcriptomics evidence supported a response to HS in the rat retina that was affected by age and sex. Several molecular networks were identified that suggest stress imposed by HS affected the retinal vasculature, oxidative and inflammation status, pigmented epithelium function, and glial activation. The CSNK1A1-TP53 pathway was implicated in the response in all cohorts. The most significant gender-specific genes were involved in cytoprotection, eye development and function, and may explain gender-dependent vulnerabilities to certain eye diseases. The results presented constitute the conclusion of this study and support the hypothesis that underlying changes in the biology of the retina subjected to simulated microgravity involve both the neural and vascular retina.
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Articles in Peer-reviewed Journals
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Theriot CA, Chevez-Barrios P, Loughlin T, Beheshti A, Mercaldo ND, Zanello SB. "The impact of hindlimb suspension on the rat eye: A molecular and histological analysis of the retina." Gravit Space Res. 2021 Sep 17;9(1):86-103. https://doi.org/10.2478/gsr-2021-0007
, Sep-2021
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Articles in Peer-reviewed Journals
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Lagatuz M, Vyas RJ, Predovic M, Lim S, Jacobs N, Martinho M, Valizadegan H, Kao D, Oza N, Theriot CA, Zanello SB, Taibbi G, Vizzeri G, Dupont M, Grant MB, Lindner DJ, Reinecker HC, Pinhas A, Chui TY, Rosen RB, Moldovan N, Vickerman MB, Radhakrishnan K, Parsons-Wingerter P. "Vascular patterning as integrative readout of complex molecular and physiological signaling by VESsel GENeration Analysis." J Vasc Res. 2021 Jul;58(4):207-30. Review. https://doi.org/10.1159/000514211 ; PMID: 33839725 , Jul-2021
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Articles in Peer-reviewed Journals
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da Silveira WA, Fazelinia H, Rosenthal SB, Laiakis EC, Kim MS, Meydan C, Kidane Y, Rathi KS, Smith SM, Stear B, Ying Y, Zhang Y, Foox J, Zanello S, Crucian B, Wang D, Nugent A, Costa HA, Zwart SR, Schrepfer S, Elworth RAL, Sapoval N, Treangen T, MacKay M, Gokhale NS, Horner SM, Singh LN, Wallace DC, Willey JS, Schisler JC, Meller R, McDonald JT, Fisch KM, Hardiman G, Taylor D, Mason CE, Costes SV, Beheshti A. "Comprehensive multi-omics analysis reveals mitochondrial stress as a central biological hub for spaceflight impact." Cell. 2020 Nov 25;183(5):1185-201.e20. https://doi.org/10.1016/j.cell.2020.11.002 ; PMID: 33242417; PMCID: PMC7870178 , Nov-2020
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Articles in Peer-reviewed Journals
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Vyas RJ, Young M, Murray MC, Predovic M, Lim S, Jacobs NM, Mason SS, Zanello SB, Taibbi G, Vizzeri G, Parsons-Wingerter P. "Decreased vascular patterning in the retinas of astronaut crew members as new measure of ocular damage in spaceflight-associated neuro-ocular syndrome." Invest Ophthalmol Vis Sci. 2020 Dec 1;61(14):34. https://doi.org/10.1167/iovs.61.14.34 ; PMID: 33372980; PMCID: PMC7774106 , Dec-2020
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