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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,11,12]]},"abstract":"<jats:p>\n                    The choroid is the thin, vasculature-filled layer of the eye situated between the sclera and the retina, where it serves the metabolic needs of the light-sensing photoreceptors in the retina. Illumination of the interior surface of the back of the eye (fundus) is a critical regulator of subretinal fluid homeostasis, which determines the overall shape of the eye, but it is also important for choroidal perfusion. Noted for having some of the highest blood flow rates in the body, the choroidal vasculature has been reported to lack intrinsic, intravascular pressure-induced (myogenic) autoregulatory mechanisms. Here, we ask how light directly regulates choroid perfusion and ocular fluid homeostasis, testing the hypothesis that light facilitates ocular fluid absorption by directly increasing choroid endothelial permeability and decreasing choroid perfusion. Utilizing ex vivo pressurized whole-choroid and whole-eye preparations from mice expressing cell-specific Ca\n                    <jats:sup>2+<\/jats:sup>\n                    indicators, we found that the choroidal vasculature has two intrinsically light-sensitive Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -signaling mechanisms: One increases Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -dependent production of nitric oxide in choroidal endothelial cells; the other promotes vasoconstriction through Ca\n                    <jats:sup>2+<\/jats:sup>\n                    elevation in vascular smooth muscle cells. In addition, we found that choroidal flow, or pressure, modulates endothelial and smooth muscle photosensitivity and trans-retinal absorption of fluid into the choroid. These results collectively suggest that the choroid vasculature exhibits an inverted form of autoregulatory control, where pressure- and light-induced mechanisms work in opposition to regulate blood flow and maintain fluid balance in response to changes in light and dark, aligning with the metabolic needs of photoreceptors.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2418429121","type":"journal-article","created":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T11:44:53Z","timestamp":1731066293000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":6,"title":["Light-sensitive Ca\n                    <sup>2+<\/sup>\n                    signaling in the mammalian choroid"],"prefix":"10.1073","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1351-9261","authenticated-orcid":false,"given":"Ahmed M.","family":"Eltanahy","sequence":"first","affiliation":[{"name":"Department of Physiology and Cell Biology, Center for Molecular and Cellular Signaling in the Cardiovascular System, University of Nevada, Reno School of Medicine, Reno, NV 89557-0318"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Aupetit","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology, Center for Molecular and Cellular Signaling in the Cardiovascular System, University of Nevada, Reno School of Medicine, Reno, NV 89557-0318"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethan D.","family":"Buhr","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Washington, Seattle, WA 98104"},{"name":"Roger and Angie Karalis Retina Center, Department of Ophthalmology, University of Washington, Seattle, WA 98104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell N.","family":"Van Gelder","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Washington, Seattle, WA 98104"},{"name":"Roger and Angie Karalis Retina Center, Department of Ophthalmology, University of Washington, Seattle, WA 98104"},{"name":"Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98104"},{"name":"Department of Neurobiology &amp; Biophysics, University of Washington, Seattle, WA 98104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5382-8712","authenticated-orcid":false,"given":"Albert L.","family":"Gonzales","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology, Center for Molecular and Cellular Signaling in the Cardiovascular System, University of Nevada, Reno School of Medicine, Reno, NV 89557-0318"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2024,11,8]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.aanat.2024.152239"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.99.2.177"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4835(73)90185-1"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/eye.1990.43"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.1979.tb06409.x"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplegacy.1963.205.1.60"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.1970.tb04765.x"},{"key":"e_1_3_4_8_2","first-page":"417","article-title":"Arteriovenous oxygen difference across the uveal tract of the dog eye","volume":"3","author":"Elgin S. 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