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O2 uptake from the atmosphere accounts for virtually all the O2 consumption in the avascular cornea; however, a detailed spatiotemporal profile of corneal O2 uptake (COU) remains undetermined. Here, we used a non-invasive self-referencing optical fiber O2 sensor\u2014the scanning micro-optrode technique (SMOT)\u2014to report the O2 partial pressure and flux variations at the ocular surface of rodents and non-human primates. In vivo spatial mapping in mice revealed a distinct COU, characterized by a centripetal gradient with a significantly higher O2 influx at the limbus and conjunctiva regions than at the center of the cornea. This regional COU profile was reproduced ex vivo in freshly enucleated eyes. The centripetal gradient was conserved across the following species analyzed: mice, rats, and rhesus monkeys. In vivo temporal mapping in mice showed a significant increase in the O2 flux in the limbus in the evening compared to other times. Altogether, the data unveiled a conserved centripetal COU profile, which may be associated with the limbal epithelial stem cells residing at the intersection of the limbus and conjunctiva. These physiological observations will serve as a useful baseline for comparative studies with contact lens wear, ocular disease, diabetes, etc. Moreover, the sensor may be applied to understand the responses of the cornea and other tissues to various insults, drugs, or changes in the environment.<\/jats:p>","DOI":"10.3390\/bios13020245","type":"journal-article","created":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T01:59:43Z","timestamp":1675907983000},"page":"245","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Optic Fiber Microsensor Reveals Specific Spatiotemporal Oxygen Uptake Profiles at the Mammalian Ocular Surface"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7190-6462","authenticated-orcid":false,"given":"Qin","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Dermatology, Institute for Regenerative Cures, School of Medicine, University of California, Davis, CA 95816, USA"},{"name":"School of Life Science, Yunnan Normal University, Kunming 650092, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Institute for Regenerative Cures, School of Medicine, University of California, Davis, CA 95816, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5786-8896","authenticated-orcid":false,"given":"Fernando","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Institute for Regenerative Cures, School of Medicine, University of California, Davis, CA 95816, USA"},{"name":"Departamento de Biologia, Centro de Biologia Molecular e Ambiental (CMBA), Universidade do Minho, 4710-057 Braga, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chelsea","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology & Vision Science, Institute for Regenerative Cures, School of Medicine, University of California, Davis, CA 95816, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2966-1251","authenticated-orcid":false,"given":"Brian","family":"Reid","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Institute for Regenerative Cures, School of Medicine, University of California, Davis, CA 95816, USA"},{"name":"Department of Ophthalmology & Vision Science, Institute for Regenerative Cures, School of Medicine, University of California, Davis, CA 95816, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2500-3035","authenticated-orcid":false,"given":"Min","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Institute for Regenerative Cures, School of Medicine, University of California, Davis, CA 95816, USA"},{"name":"Department of Ophthalmology & Vision Science, Institute for Regenerative Cures, School of Medicine, University of California, Davis, CA 95816, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BJ20070389","article-title":"Oxygen-dependent regulation of mitochondrial respiration by hypoxia-inducible factor 1","volume":"405","author":"Semenza","year":"2007","journal-title":"Biochem. J."},{"key":"ref_2","first-page":"147","article-title":"Effect of hypoxia on the proliferation of murine cornea limbal epithelial progenitor cells in vitro","volume":"4","author":"Ma","year":"2011","journal-title":"Int. J. Ophthalmol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4296","DOI":"10.1038\/s41467-018-06614-2","article-title":"Early redox activities modulate Xenopus tail regeneration","volume":"9","author":"Ferreira","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_4","first-page":"1","article-title":"Partial pressure of oxygen in the human body: A general review","volume":"9","author":"Dunn","year":"2019","journal-title":"Am. J. blood Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1111\/j.1582-4934.2011.01258.x","article-title":"Why is the partial oxygen pressure of human tissues a crucial parameter? Small molecules and hypoxia","volume":"15","author":"Carreau","year":"2011","journal-title":"J. Cell. Mol. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/nrm2354","article-title":"The role of oxygen availability in embryonic development and stem cell function","volume":"9","author":"Simon","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_7","first-page":"2170","article-title":"The effect of hypoxia on endogenous corneal epithelial eicosanoids","volume":"41","author":"Mieyal","year":"2000","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1113\/jphysiol.1972.sp009927","article-title":"Oxygen consumption by the component layers of the cornea","volume":"225","author":"Freeman","year":"1972","journal-title":"J. Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1167\/iovs.16-21154","article-title":"Modulation of Circadian Rhythms Affects Corneal Epithelium Renewal and Repair in Mice","volume":"58","author":"Xue","year":"2017","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1002\/ame2.12192","article-title":"Hypoxia adaptation in the cornea: Current animal models and underlying mechanisms","volume":"4","author":"Pang","year":"2021","journal-title":"Anim. Model. Exp. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6331","DOI":"10.1167\/iovs.12-10059","article-title":"In Vivo Oxygen Uptake into the Human Cornea","volume":"53","author":"Takatori","year":"2012","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1111\/j.1444-0938.1986.tb04579.x","article-title":"Oxygen uptake profile of the human cornea","volume":"69","author":"Fitzgerald","year":"1986","journal-title":"Clin. Exp. Optom."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1167\/iovs.61.11.1","article-title":"Diurnal Control of Sensory Axon Growth and Shedding in the Mouse Cornea","volume":"61","author":"Tadvalkar","year":"2020","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/s41596-019-0231-x","article-title":"Real-time physiological measurements of oxygen using a non-invasive self-referencing optical fiber microsensor","volume":"15","author":"Ferreira","year":"2020","journal-title":"Nat. Protoc."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"32871","DOI":"10.1038\/srep32871","article-title":"Insulin Restores an Altered Corneal Epithelium Circadian Rhythm in Mice with Streptozotocin-induced Type 1 Diabetes","volume":"6","author":"Song","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_16","first-page":"371","article-title":"Estimation of human corneal oxygen consumption by noninvasive measurement of tear oxygen tension while wearing hydrogel lenses","volume":"43","author":"Bonanno","year":"2002","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1002\/bies.201500002","article-title":"Luminescent sensing and imaging of oxygen: Fierce competition to the Clark electrode","volume":"37","author":"Wolfbeis","year":"2015","journal-title":"Bioessays"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5528","DOI":"10.1364\/AO.48.005528","article-title":"Frequency-domain fluorescence lifetime optrode system design and instrumentation without a concurrent reference light-emitting diode","volume":"48","author":"Chatni","year":"2009","journal-title":"Appl. Opt."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1016\/j.stem.2021.04.003","article-title":"Discrete limbal epithelial stem cell populations mediate corneal homeostasis and wound healing","volume":"28","author":"Altshuler","year":"2021","journal-title":"Cell Stem Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1007\/s00425-013-1926-9","article-title":"Emerging technologies for non-invasive quantification of physiological oxygen transport in plants","volume":"238","author":"Chaturvedi","year":"2013","journal-title":"Planta"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1152\/jappl.1958.13.1.85","article-title":"Chronically Implanted Polarographic Electrodes","volume":"13","author":"Clark","year":"1958","journal-title":"J. Appl. Physiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/BF02150573","article-title":"Human cornea: Oxygen uptake immediately following graded deprivation","volume":"223","author":"Benjamin","year":"1985","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_23","first-page":"1899","article-title":"Measuring oxygen tension in the anterior chamber of rabbits","volume":"39","author":"McLaren","year":"1998","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2224","DOI":"10.1039\/b903092a","article-title":"Self-referencing optrode technology for non-invasive real-time measurement of biophysical flux and physiological sensing","volume":"134","author":"Chatni","year":"2019","journal-title":"Analyst"}],"container-title":["Biosensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6374\/13\/2\/245\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:27:52Z","timestamp":1760120872000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6374\/13\/2\/245"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,9]]},"references-count":24,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["bios13020245"],"URL":"https:\/\/doi.org\/10.3390\/bios13020245","relation":{},"ISSN":["2079-6374"],"issn-type":[{"value":"2079-6374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,9]]}}}