{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T04:51:31Z","timestamp":1790052691873,"version":"4.0.1"},"reference-count":96,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T00:00:00Z","timestamp":1710979200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Vision relies on the continuous exchange of material between the photoreceptors, retinal pigment epithelium and choriocapillaris, a dense microvascular bed located underneath the outer retina. The anatomy and physiology of the choriocapillaris and their association with retinal homeostasis have proven difficult to characterize, mainly because of the unusual geometry of this vascular bed. By analysing tissue dissected from 81 human eyes, we show that the thickness of the choriocapillaris does not vary significantly over large portions of the macula or with age. Assessments of spatial variations in the anatomy of the choriocapillaris in three additional human eyes indicate that the location of arteriolar and venular vessels connected to the plane of the choriocapillaris is non\u2010random, and that venular insertions cluster around arteriolar ones. Mathematical models built upon these anatomical analyses reveal that the choriocapillaris contains regions where the transport of passive elements is dominated by diffusion, and that these diffusion\u2010limited regions represent areas of reduced exchange with the outer retina. The width of diffusion\u2010limited regions is determined by arterial flow rate and the relative arrangement of arteriolar and venular insertions. These analyses demonstrate that the apparent complexity of the choriocapillaris conceals a fine balance between several anatomical and functional parameters to effectively support homeostasis of the outer retina.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp15996-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>The choriocapillaris is the capillary bed supporting the metabolism of photoreceptors and retinal pigment epithelium, two critical components of the visual system located in the outer part of the retina.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The choriocapillaris has evolved a planar multipolar vascular geometry that differs markedly from the branched topology of most vasculatures in the human body.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Here, we report that this planar multipolar vascular geometry is associated with spatially heterogenous molecular exchange between choriocapillaris and outer retina.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Our data and analyses highlight a necessary balance between choriocapillaris anatomical and functional parameters to effectively support homeostasis of the outer retina.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp285050","type":"journal-article","created":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T14:10:17Z","timestamp":1711030217000},"page":"1273-1295","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The vascular geometry of the choriocapillaris is associated with spatially heterogeneous molecular exchange with the outer retina"],"prefix":"10.1113","volume":"602","author":[{"given":"Caitlin D.","family":"Faust","sequence":"first","affiliation":[{"name":"John A. Moran Eye Center Department of Ophthalmology &amp; Visual Sciences University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian A.","family":"Klettner","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Toso","sequence":"additional","affiliation":[{"name":"John A. Moran Eye Center Department of Ophthalmology &amp; Visual Sciences University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory S.","family":"Hageman","sequence":"additional","affiliation":[{"name":"John A. Moran Eye Center Department of Ophthalmology &amp; Visual Sciences University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1300-5738","authenticated-orcid":false,"given":"Ian","family":"Eames","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip J.","family":"Luthert","sequence":"additional","affiliation":[{"name":"Institute of Ophthalmology University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3689-7748","authenticated-orcid":false,"given":"Moussa A.","family":"Zouache","sequence":"additional","affiliation":[{"name":"John A. Moran Eye Center Department of Ophthalmology &amp; Visual Sciences University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,21]]},"reference":[{"issue":"7","key":"e_1_2_5_2_1","first-page":"36","article-title":"Image processing with imageJ","volume":"11","author":"Abramoff M. D.","year":"2004","journal-title":"Biophotonics International"},{"key":"e_1_2_5_3_1","volume-title":"Handbook of Mathematical Functions: With Formulas, Graphs, and Mathematical Tables, 9th printing","author":"Abramowitz M.","year":"1972"},{"key":"e_1_2_5_4_1","first-page":"315","article-title":"Observations on the corrosion casts of the choriocapillaries","volume":"80","author":"Araki M.","year":"1976","journal-title":"Acta Societatis Ophthalmologicae Japonicae"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9394(70)91619-3"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.36.9.465"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1201\/b19708"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v012.i06"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00127638"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2LC01033J"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9394(99)00061-6"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0361-9230(81)90007-1"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9394(61)91796-2"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0025-5564(78)90044-5"},{"issue":"7","key":"e_1_2_5_15_1","first-page":"1247","article-title":"Variability in choriocapillaris blood flow distribution","volume":"36","author":"Flower R. W.","year":"1995","journal-title":"Investigative Ophthalmology & Visual Science"},{"issue":"9","key":"e_1_2_5_16_1","first-page":"2720","article-title":"Extraction of choriocapillaris hemodynamic data from ICG fluorescence angiograms","volume":"34","author":"Flower R. W.","year":"1993","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1963.00960040226014"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1985.01050010124034"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02280087"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00224463"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1159\/000146586"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00915961"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10384-007-0474-x"},{"key":"e_1_2_5_24_1","first-page":"545","article-title":"The ultrastructure of the retinal pigment epithelium with observations on the choriocapillaris and Bruch's membrane","volume":"61","author":"Garron L. K.","year":"1963","journal-title":"Transactions of the American Ophthalmological Society"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/nme.2579"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09740-7"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4835(74)90078-5"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.58.4.391"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00416864"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.59.11.631"},{"key":"e_1_2_5_31_1","volume-title":"Global Health Estimates: Deaths by Cause, Age, Sex and Country, 2000\u20132012","author":"Health Organisation W.","year":"2014"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/aic.690140628"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.03-0759"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9394(61)91797-4"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9394(69)90987-8"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.49.4.663"},{"issue":"10","key":"e_1_2_5_37_1","first-page":"3724","article-title":"Noninvasive visualization of the choriocapillaris and its dynamic filling","volume":"35","author":"Kiryu J.","year":"1994","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9394(66)90243-1"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevE.50.4650"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1919.sp001839"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1919.sp001844"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.868075"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.36.1.148"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2396104"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0022112072001557"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1515\/REVAC.1999.18.1-2.23"},{"key":"e_1_2_5_47_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.99.2.177"},{"key":"e_1_2_5_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2017.01.003"},{"key":"e_1_2_5_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.105755"},{"key":"e_1_2_5_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-3768.2008.01247.x"},{"key":"e_1_2_5_51_1","doi-asserted-by":"publisher","DOI":"10.1115\/1.3645793"},{"key":"e_1_2_5_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02720657"},{"key":"e_1_2_5_53_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.10-6476"},{"key":"e_1_2_5_54_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.12.3.207"},{"key":"e_1_2_5_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00348-001-0370-y"},{"key":"e_1_2_5_56_1","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.017574"},{"key":"e_1_2_5_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/eye.1990.38"},{"key":"e_1_2_5_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/eye.1991.32"},{"key":"e_1_2_5_59_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.117.10.1353"},{"key":"e_1_2_5_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9394(77)90852-2"},{"key":"e_1_2_5_61_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.75.5.904"},{"key":"e_1_2_5_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms1471"},{"issue":"6","key":"e_1_2_5_63_1","first-page":"2857","article-title":"Morphometric analysis of Bruch's membrane, the choriocapillaris, and the choroid in aging","volume":"35","author":"Ramrattan R. S.","year":"1994","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"e_1_2_5_64_1","first-page":"445","article-title":"Note sur les Vaisseaux Sanguins et la circulation dans les muscles rouges","volume":"1","author":"Ranvier L.","year":"1874","journal-title":"Arch Physiology Norm Path"},{"key":"e_1_2_5_65_1","volume-title":"The Anatomy and Histology of the Human Eyeball in the Normal State, Its Development and Senescence","author":"Salzman M.","year":"1912"},{"key":"e_1_2_5_66_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaophthalmol.2016.3519"},{"key":"e_1_2_5_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(67)86624-4"},{"key":"e_1_2_5_68_1","article-title":"Die Vertheilung der Blutgefasse in Muskel","author":"Spalteholtz W.","year":"1888","journal-title":"Abh S\u00e4chs Ges Wiss Math Phys"},{"key":"e_1_2_5_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0039-6257(99)00086-7"},{"issue":"13","key":"e_1_2_5_70_1","first-page":"2724","article-title":"Morphometric analysis of the choroid, Bruch's membrane, and retinal pigment epithelium in eyes with age\u2010related macular degeneration","volume":"37","author":"Spraul C. W.","year":"1996","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"e_1_2_5_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0042-6989(02)00022-6"},{"key":"e_1_2_5_72_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.50.1.21"},{"issue":"2","key":"e_1_2_5_73_1","first-page":"191","article-title":"Effect of raised intraocular pressure on the retinal and choroidal circulation","volume":"7","author":"Dollery C. T.","year":"1968","journal-title":"Investigative Ophthalmology & Visual Science"},{"issue":"10","key":"e_1_2_5_74_1","first-page":"2844","article-title":"Evaluation of leukocyte dynamics in choroidal circulation with indocyanine green\u2013stained leukocytes","volume":"41","author":"Takasu I.","year":"2000","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"e_1_2_5_75_1","unstructured":"Team R. C.(2021). R: A Language and Environment for Statistical Computing."},{"key":"e_1_2_5_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9394(76)90298-1"},{"key":"e_1_2_5_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(85)33992-1"},{"key":"e_1_2_5_78_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00137959"},{"key":"e_1_2_5_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9150(76)90029-0"},{"issue":"1","key":"e_1_2_5_80_1","first-page":"48","article-title":"Glucose metabolism in cat outer retina. Effects of light and hyperoxia","volume":"38","author":"Wang L.","year":"1997","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"e_1_2_5_81_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-201X.1997.00131.x"},{"key":"e_1_2_5_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9394(14)76294-4"},{"key":"e_1_2_5_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.survophthal.2018.03.003"},{"key":"e_1_2_5_84_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5309.122"},{"key":"e_1_2_5_85_1","volume-title":"The Retinal Circulation","author":"Wise G. N.","year":"1975"},{"key":"e_1_2_5_86_1","doi-asserted-by":"publisher","DOI":"10.2147\/EB.S9078"},{"key":"e_1_2_5_87_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(13)70145-1"},{"key":"e_1_2_5_88_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.38.9.513"},{"issue":"1","key":"e_1_2_5_89_1","first-page":"94","article-title":"A study of the choroidal circulation of the eye in man","volume":"88","author":"Wybar K. C.","year":"1954","journal-title":"Journal of Anatomy"},{"key":"e_1_2_5_90_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00127637"},{"key":"e_1_2_5_91_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1966.21.3.915"},{"key":"e_1_2_5_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/1350-9462(94)90012-4"},{"key":"e_1_2_5_93_1","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevE.56.4244"},{"key":"e_1_2_5_94_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep35754"},{"key":"e_1_2_5_95_1","doi-asserted-by":"publisher","DOI":"10.1017\/jfm.2018.771"},{"key":"e_1_2_5_96_1","doi-asserted-by":"publisher","DOI":"10.1017\/jfm.2015.243"},{"key":"e_1_2_5_97_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.778404"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP285050","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T03:21:51Z","timestamp":1711941711000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/JP285050"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,21]]},"references-count":96,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["10.1113\/JP285050"],"URL":"https:\/\/doi.org\/10.1113\/jp285050","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,21]]},"assertion":[{"value":"2023-07-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}