{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:59:13Z","timestamp":1787018353769,"version":"build-2736575974"},"reference-count":50,"publisher":"American Society for Clinical Investigation","issue":"22","license":[{"start":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T00:00:00Z","timestamp":1763942400000},"content-version":"vor","delay-in-days":41,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"canadian institute of health","award":["PJT-175160"],"award-info":[{"award-number":["PJT-175160"]}]},{"name":"NIH","award":["R01EY024261"],"award-info":[{"award-number":["R01EY024261"]}]},{"name":"NIH","award":["R01EY033316"],"award-info":[{"award-number":["R01EY033316"]}]},{"name":"NIH","award":["R21DA056728"],"award-info":[{"award-number":["R21DA056728"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,24]]},"abstract":"<jats:p>\n                    Macular edema (ME) can cause profound vision impairment and occurs in several prevalent retinal diseases, including diabetic retinopathy, choroidal neovascularization, retinal vein occlusion, and uveitis. Retinal edema typically results from dysfunction of the blood-retina barrier (BRB), which is associated with increased retinal expression of complement components. It is unclear whether the classical complement pathway has detrimental or protective roles in the context of BRB dysfunction. Here, we characterized\n                    <jats:italic>Tspan12<\/jats:italic>\n                    -KO\n                    <jats:sup>DBM<\/jats:sup>\n                    (disrupted BRB maintenance) mice, a mouse model of cystoid edema generated by genetically and pharmacologically manipulating \u03b2-catenin\u2013dependent norrin\/frizzled-4 (FZD4) signaling. We assessed BRB function, cystoid edema, electroretinogram, and microglia activation outcomes in an aging study with WT,\n                    <jats:italic>C1qa<\/jats:italic>\n                    -KO,\n                    <jats:italic>Tspan12<\/jats:italic>\n                    -KO\n                    <jats:sup>DBM<\/jats:sup>\n                    , and\n                    <jats:italic>Tspan12<\/jats:italic>\n                    -KO\n                    <jats:sup>DBM<\/jats:sup>\n                    <jats:italic>; C1qa<\/jats:italic>\n                    -KO compound mutant mice. Phenotypic analyses and cell-based experiments indicated that C1QA contributes to maintaining basal \u03b2-catenin\u2013dependent signaling and that the absence of C1QA exacerbates BRB dysfunction, cystoid edema, and neuroinflammation in\n                    <jats:italic>Tspan12<\/jats:italic>\n                    -KO\n                    <jats:sup>DBM<\/jats:sup>\n                    <jats:italic>; C1qa<\/jats:italic>\n                    -KO compound mutant mice. Activation of \u03b2-catenin\u2013dependent signaling by an anti-FZD4 and anti-LRP5 agonistic antibody modality achieved complete resolution of cystoid edema. This study shows that reducing or enhancing norrin\/FZD4 signaling can increase or decrease cystoid edema, respectively, underscoring its potential as a therapeutic target in ME. Furthermore, this study provides insights into the contribution of C1QA to BRB maintenance.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.190227","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T16:00:29Z","timestamp":1760457629000},"source":"Crossref","is-referenced-by-count":2,"title":["C1q limits cystoid edema by maintaining basal \u03b2-catenin\u2013dependent signaling and blood-retina barrier function"],"prefix":"10.1172","volume":"10","author":[{"given":"Lingling","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, Minnesota, USA."},{"name":"Department of Biology, University of St. Thomas, Saint Paul, Minnesota, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacklyn","family":"Levey","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, Minnesota, USA."},{"name":"Graduate Program in Molecular, Cellular, Developmental Biology and Genetics, University of Minnesota, Minneapolis, Minnesota, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md.","family":"Abedin","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, Minnesota, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2602-5754","authenticated-orcid":true,"given":"Ha-Neul","family":"Jo","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, Minnesota, USA."},{"name":"Graduate Program in Molecular, Cellular, Developmental Biology and Genetics, University of Minnesota, Minneapolis, Minnesota, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Odame","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, Minnesota, USA."},{"name":"Graduate Program in Molecular, Cellular, Developmental Biology and Genetics, University of Minnesota, Minneapolis, Minnesota, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miranda","family":"Howe","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, Minnesota, USA."},{"name":"Graduate Program in Molecular, Cellular, Developmental Biology and Genetics, University of Minnesota, Minneapolis, Minnesota, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaia L.","family":"Douglas","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Neurosciences, University of 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