{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T16:12:33Z","timestamp":1781712753885,"version":"3.54.5"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,7,20]],"date-time":"2023-07-20T00:00:00Z","timestamp":1689811200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p><jats:bold>Objective:<\/jats:bold> Microgravity contributes to ocular injury yet the underlying mechanism remains unclear. This study aims to elucidate the mechanism behind choroidal circulation disorder and outer retinal degeneration in rats with simulated weightlessness.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Optical coherence tomography angiography (OCTA) was used to evaluate choroidal circulation and retinal morphological alterations in rats with weightlessness simulation. Electroretinogram and transmission electron microscopy were used to examine the ultrastructure and function of the choroid and outer retina. Furthermore, histological and terminal deoxynucleotidyl transferase deoxyuridine dUTP nick-end labeling (TUNEL) staining was used to monitor retinal morphology. Western blotting was performed to analyze the expressions of blood-retinal outer barrier function-related proteins (Cx43, ZO-1, and occludin).<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> The choroidal thickening was observed from the fourth week of simulated weightlessness (<jats:italic>p<\/jats:italic> &amp;lt; 0.05), and choroidal capillary density started to decline by the fifth week (<jats:italic>p<\/jats:italic> &amp;lt; 0.05). Transmission electron microscopy revealed that the choroidal vessels were open and operating well by the fourth week. However, most of the mitochondria within the vascular endothelium underwent mild swelling, and by the fifth week, the choroidal vessels had various degrees of erythrocyte aggregation, mitochondrial swelling, and apoptosis. Additionally, ERG demonstrated a decline in retinal function beginning in the fifth week (<jats:italic>p<\/jats:italic> &amp;lt; 0.05). TUNEL staining revealed a significantly higher apoptotic index in the outer nuclear layer of the retina (<jats:italic>p<\/jats:italic> &amp;lt; 0.05). At the sixth week\u00a0weeks of simulated weightlessness, OCTA and hematoxylin and eosin (HE) staining of retinal sections revealed that the outer nuclear layer of the retina started to become thin (<jats:italic>p<\/jats:italic> &amp;lt; 0.05). Results from western blotting revealed that Cx43, ZO-1, and occludin exhibited decreased expression (<jats:italic>p<\/jats:italic> &amp;lt; 0.05).<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Based on our findings in a rat model of simulated weightlessness, choroidal circulation disturbance induced by choroidal congestion is the initial cause of outer retinal degeneration. Blood-retinal barrier disruption is significant in this process.<\/jats:p>","DOI":"10.3389\/fphys.2023.1198862","type":"journal-article","created":{"date-parts":[[2023,7,20]],"date-time":"2023-07-20T11:49:35Z","timestamp":1689853775000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Choroidal circulation disturbance is an initial factor in outer retinal degeneration in rats under simulated weightlessness"],"prefix":"10.3389","volume":"14","author":[{"given":"Yuxue","family":"Mu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongyu","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilingxuan","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyue","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruidan","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuoming","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,7,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1016\/j.expneurol.2019.03.014","article-title":"Impairment of pericyte-endothelium crosstalk leads to blood-brain barrier dysfunction following traumatic brain injury","volume":"317","author":"Bhowmick","year":"2019","journal-title":"Exp. Neurol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"119","DOI":"10.3233\/CH-170366","article-title":"Analysis of human microcirculation in weightlessness: Study protocol and pre-study experiments","volume":"70","author":"Bimpong-Buta","year":"2018","journal-title":"Clin. Hemorheol. Microcirc."},{"key":"B3","doi-asserted-by":"publisher","first-page":"960","DOI":"10.3389\/fphys.2020.00960","article-title":"Comprehensive analysis of macrocirculation and microcirculation in microgravity during parabolic flights","volume":"11","author":"Bimpong-Buta","year":"2020","journal-title":"Front. Physiol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/j.bbamcr.2003.08.003","article-title":"Endothelial stress by gravitational unloading: Effects on cell growth and cytoskeletal organization","volume":"1642","author":"Carlsson","year":"2003","journal-title":"Biochim. Biophys. Acta"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000452520","article-title":"Reduced expression of cytoskeletal and extracellular matrix genes in human adult retinal pigment epithelium cells exposed to simulated microgravity","volume":"40","author":"Corydon","year":"2016","journal-title":"Cell Physiol. Biochem."},{"key":"B6","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.bbamcr.2005.10.002","article-title":"Impact of modeled microgravity on microvascular endothelial cells","volume":"1746","author":"Cotrupi","year":"2005","journal-title":"Biochim. Biophys. Acta"},{"key":"B7","doi-asserted-by":"publisher","first-page":"H1866","DOI":"10.1152\/ajpheart.2000.278.6.H1866","article-title":"Structural and functional remodeling of skeletal muscle microvasculature is induced by simulated microgravity","volume":"278","author":"Delp","year":"2000","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1177\/15353702221139189","article-title":"Impacts of microgravity on amino acid metabolism during spaceflight","volume":"248","author":"Dickerson","year":"2023","journal-title":"Exp. Biol. Med. (Maywood)."},{"key":"B9","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/j.tins.2008.02.008","article-title":"The mitochondrial impairment, oxidative stress and neurodegeneration connection: Reality or just an attractive hypothesis?","volume":"31","author":"Fukui","year":"2008","journal-title":"Trends Neurosci."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1641717","DOI":"10.1155\/2021\/1641717","article-title":"ALDH2\/SIRT1 contributes to type 1 and type 2 diabetes-induced retinopathy through depressing oxidative stress","volume":"2021","author":"He","year":"2021","journal-title":"Oxid. Med. Cell Longev."},{"key":"B11","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1016\/j.bbrc.2018.05.060","article-title":"Long-term hindlimb unloading causes a preferential reduction of medullary thymic epithelial cells expressing autoimmune regulator (Aire)","volume":"501","author":"Horie","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B12","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1139\/apnm-2016-0363","article-title":"Tetramethylpyrazine ameliorated disuse-induced gastrocnemius muscle atrophy in hindlimb unloading rats through suppression of Ca2+\/ROS-mediated apoptosis","volume":"42","author":"Hu","year":"2017","journal-title":"Appl. Physiol. Nutr. Metab."},{"key":"B13","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1097\/IJG.0000000000001293","article-title":"Gravitational influence on intraocular pressure: Implications for spaceflight and disease","volume":"28","author":"Huang","year":"2019","journal-title":"J. Glaucoma"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1436","DOI":"10.1038\/s41467-022-29139-1","article-title":"LC3B is an RNA-binding protein to trigger rapid mRNA degradation during autophagy","volume":"13","author":"Hwang","year":"2022","journal-title":"Nat. Commun."},{"key":"B15","doi-asserted-by":"publisher","first-page":"169","DOI":"10.3233\/CH-1663301","article-title":"The microcirculation in hypoxia: The center of the battlefield for oxygen","volume":"63","author":"Jung","year":"2016","journal-title":"Clin. Hemorheol. Microcirc."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1437","DOI":"10.1007\/s10792-021-02133-0","article-title":"Investigation of the pathophysiology of the retina and choroid in Parkinson's disease by optical coherence tomography","volume":"42","author":"Kamata","year":"2022","journal-title":"Int. Ophthalmol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1097\/ICU.0000000000000724","article-title":"Visual disturbances during prolonged space missions","volume":"32","author":"Khossravi","year":"2021","journal-title":"Curr. Opin. Ophthalmol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1581","DOI":"10.1089\/ars.2005.7.1581","article-title":"Diabetic retinopathy: Mitochondrial dysfunction and retinal capillary cell death","volume":"7","author":"Kowluru","year":"2005","journal-title":"Antioxid. Redox Signal"},{"key":"B19","doi-asserted-by":"publisher","first-page":"100951","DOI":"10.1016\/j.preteyeres.2021.100951","article-title":"Retinal applications of swept source optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA)","volume":"84","author":"La\u00edns","year":"2021","journal-title":"Prog. Retin Eye Res."},{"key":"B20","doi-asserted-by":"publisher","first-page":"109200","DOI":"10.1016\/j.exer.2022.109200","article-title":"Structural damage to the rat eye following long-term simulated weightlessness","volume":"223","author":"Li","year":"2022","journal-title":"Exp. Eye Res."},{"key":"B21","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1080\/01658107.2020.1791189","article-title":"Persistent globe flattening in astronauts following long-duration spaceflight","volume":"45","author":"Mader","year":"2020","journal-title":"Neuroophthalmology"},{"key":"B22","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/s0002-9394(14)73586-x","article-title":"Intraocular pressure and retinal vascular changes during transient exposure to microgravity","volume":"115","author":"Mader","year":"1993","journal-title":"Am. J. Ophthalmol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"S206","DOI":"10.4103\/0028-3886.259126","article-title":"An overview of spaceflight-associated neuro-ocular syndrome (SANS)","volume":"67","author":"Mader","year":"2019","journal-title":"Neurol. India"},{"key":"B24","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1667\/RR15219.1","article-title":"Combined effects of low-dose proton radiation and simulated microgravity on the mouse retina and the hematopoietic system","volume":"192","author":"Mao","year":"2019","journal-title":"Radiat. Res."},{"key":"B25","doi-asserted-by":"publisher","first-page":"e1915011","DOI":"10.1001\/jamanetworkopen.2019.15011","article-title":"Assessment of jugular venous blood flow stasis and thrombosis during spaceflight","volume":"2","author":"Marshall-Goebel","year":"2019","journal-title":"JAMA Netw. Open"},{"key":"B26","doi-asserted-by":"publisher","first-page":"105","DOI":"10.2147\/EB.S234076","article-title":"Spaceflight associated neuro-ocular syndrome (SANS): A systematic review and future directions","volume":"12","author":"Martin Paez","year":"2020","journal-title":"Eye Brain"},{"key":"B27","doi-asserted-by":"publisher","first-page":"621","DOI":"10.3390\/life4040621","article-title":"Microgravity-induced fluid shift and ophthalmic changes","volume":"4","author":"Nelson","year":"2014","journal-title":"Life (Basel)"},{"key":"B28","doi-asserted-by":"publisher","first-page":"119384","DOI":"10.1016\/j.bbamcr.2022.119384","article-title":"Protective effect of TPP-Niacin on microgravity-induced oxidative stress and mitochondrial dysfunction of retinal epithelial cells","volume":"1870","author":"Nguyen","year":"2023","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"B29","doi-asserted-by":"publisher","first-page":"13304","DOI":"10.1038\/s41598-019-49453-x","article-title":"Spaceflight influences gene expression, photoreceptor integrity, and oxidative stress-related damage in the murine retina","volume":"9","author":"Overbey","year":"2019","journal-title":"Sci. Rep."},{"key":"B30","doi-asserted-by":"publisher","first-page":"9373","DOI":"10.3390\/ijms21249373","article-title":"Influence of microgravity on apoptosis in cells, tissues, and other systems in vivo and in vitro","volume":"21","author":"Prasad","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B31","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.preteyeres.2017.12.001","article-title":"Neural control of choroidal blood flow","volume":"64","author":"Reiner","year":"2018","journal-title":"Prog. Retin Eye Res."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1746","DOI":"10.1056\/NEJMoa1705129","article-title":"Effects of spaceflight onAstronaut brain structure as indicated on MRI","volume":"377","author":"Roberts","year":"2017","journal-title":"New Engl. J. Med."},{"key":"B33","doi-asserted-by":"publisher","first-page":"2171","DOI":"10.1007\/s00421-012-2548-9","article-title":"Weight, muscle and bone loss during space flight: Another perspective","volume":"113","author":"Stein","year":"2013","journal-title":"Eur. J. Appl. Physiol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"2333","DOI":"10.3390\/ijms22052333","article-title":"The emerging role of macrophages in immune system dysfunction under real and simulated microgravity conditions","volume":"22","author":"Sun","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B35","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1038\/s41526-021-00165-5","article-title":"Opposite response of blood vessels in the retina to 6\u00b0 head-down tilt and long-duration microgravity","volume":"7","author":"Taibbi","year":"2021","journal-title":"NPJ Microgravity"},{"key":"B36","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1167\/iovs.61.6.54","article-title":"Longitudinal structural and microvascular observation in RCS rat eyes using optical coherence tomography angiography","volume":"61","author":"Tan","year":"2020","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"B37","doi-asserted-by":"publisher","first-page":"6518","DOI":"10.1167\/iovs.13-11763","article-title":"Effects of high glucose-induced Cx43 downregulation on occludin and ZO-1 expression and tight junction barrier function in retinal endothelial cells","volume":"54","author":"Tien","year":"2013","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"B38","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1093\/pcmedi\/pbaa022","article-title":"Long-term spaceflight and the cardiovascular system","volume":"3","author":"Vernice","year":"2020","journal-title":"Precis. Clin. Med."},{"key":"B39","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1290\/0501006.1","article-title":"Activation of nuclear transcription factor-kappaB in mouse brain induced by a simulated microgravity environment","volume":"41","author":"Wise","year":"2005","journal-title":"Vitro Cell Dev. Biol. Anim."},{"key":"B40","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1167\/iovs.62.1.8","article-title":"Assessment of choroidal vascularity and choriocapillaris blood perfusion in anisomyopic adults by SS-OCT\/OCTA","volume":"62","author":"Wu","year":"2021","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"B41","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1159\/000512104","article-title":"TRPML1 inhibited photoreceptor apoptosis and protected the retina by activation of autophagy in experimental retinal detachment","volume":"64","author":"Yan","year":"2021","journal-title":"Ophthalmic Res."},{"key":"B42","doi-asserted-by":"publisher","first-page":"336","DOI":"10.18240\/ijo.2022.02.21","article-title":"Spaceflight-associated neuro-ocular syndrome: A review of potential pathogenesis and intervention","volume":"15","author":"Yang","year":"2022","journal-title":"Int. J. Ophthalmol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.lssr.2018.10.004","article-title":"Biological effects of space environmental factors: A possible interaction between space radiation and microgravity","volume":"20","author":"Yatagai","year":"2019","journal-title":"Life Sci. Space Res. (Amst)."},{"key":"B44","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1152\/physrev.00017.2016","article-title":"Spaceflight-induced intracranial hypertension and visual impairment: Pathophysiology and countermeasures","volume":"98","author":"Zhang","year":"2018","journal-title":"Physiol. Rev."},{"key":"B45","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1007\/978-1-0716-1677-2_18","article-title":"NASA's ground-based microgravity simulation facility","volume":"2368","author":"Zhang","year":"2022","journal-title":"Methods Mol. Biol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"577325","DOI":"10.3389\/fphys.2020.577325","article-title":"Effects of simulated microgravity on ultrastructure and apoptosis of choroidal vascular endothelial cells","volume":"11","author":"Zhao","year":"2021","journal-title":"Front. Physiol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"e22536","DOI":"10.1096\/fj.202200544RR","article-title":"Effects of long-term simulated microgravity on liver metabolism in rhesus macaques","volume":"36","author":"Zong","year":"2022","journal-title":"FASEB J."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2023.1198862\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,20]],"date-time":"2023-07-20T11:49:39Z","timestamp":1689853779000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2023.1198862\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,20]]},"references-count":47,"alternative-id":["10.3389\/fphys.2023.1198862"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2023.1198862","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,20]]},"article-number":"1198862"}}