{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T12:49:49Z","timestamp":1765370989660,"version":"3.46.0"},"reference-count":32,"publisher":"S. Karger AG","issue":"1","license":[{"start":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T00:00:00Z","timestamp":1748822400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T00:00:00Z","timestamp":1748822400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Ophthalmic Res"],"abstract":"<jats:p>Introduction: This study investigates the role of the immune costimulatory factor B7-H3 in laser-induced choroidal neovascularization (CNV) and its underlying molecular mechanisms. Methods: A CNV model was established in C57BL\/6J mice to examine the temporal expression dynamics of B7-H3 in choroidal tissues. B7-H3 knockout (B7-H3-KO) mice were used to assess CNV lesion size compared to wild-type (WT) controls after laser induction. RNA sequencing and xCELL analysis were performed to identify differentially expressed genes and immune cell infiltration patterns. Additionally, in vitro experiments using culture supernatants from murine B7-H3+\/\u2212 peritoneal macrophages were conducted to evaluate B7-H3\u2019s role in angiogenesis using bEnd.3 endothelial cells. Results: B7-H3 expression in the CNV model exhibited an initial upregulation followed by a decline. CNV lesions were significantly smaller in B7-H3-KO mice (1.47 \u00d7 106 \u00b1 0.21 \u00d7 106 \u00b5m2, p &lt; 0.001) and in mice receiving intravitreal injections of B7-H3 monoclonal antibody (2.29 \u00d7 106 \u00b1 0.21 \u00d7 106 \u00b5m2, p &lt; 0.05) compared to WT controls (3.46 \u00d7 106 \u00b1 0.41 \u00d7 106 \u00b5m2). Transcriptomic and xCELL analyses revealed reduced M2 macrophage infiltration and downregulation of the S100A8\/A9 heterodimer in B7-H3-KO mice. In vitro, B7-H3-KO peritoneal macrophages and RAW264.7 cells treated with S100A8\/A9-siRNA exhibited diminished proliferation, migration, and tube formation of bEnd.3 cells. These effects were reversed upon supplementation with exogenous S100A8\/A9 heterodimer to B7-H3-KO peritoneal macrophages. Further mechanistic investigation demonstrated that B7-H3 modulates bEnd.3 proliferation and CNV progression via S100A8\/A9-mediated activation of the TLR4-NF-\u03baB-VEGFA signaling pathway. Conclusion: The immune costimulatory molecule B7-H3 promotes CNV by modulating macrophage-mediated S100A8\/A9 signaling, which activates the TLR4-NF-\u03baB-VEGFA axis. These findings highlight B7-H3 as a potential therapeutic target in CNV-associated diseases.<\/jats:p>","DOI":"10.1159\/000546556","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T12:02:11Z","timestamp":1748865731000},"page":"400-418","source":"Crossref","is-referenced-by-count":0,"title":["B7-H3 Exacerbates Laser-Induced Choroidal Neovascularization by Promoting Macrophage Recruitment and Polarization via S100A8\/A9"],"prefix":"10.1159","volume":"68","author":[{"given":"Xianbin","family":"Yuan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongya","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hang","family":"Ren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiming","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingying","family":"Yao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gaoqin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peirong","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2025,6,2]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaophthalmol.2022.4401"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2017.05.035"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2020.01.029"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1016\/j.oret.2019.10.008"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2020.100906"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.49890"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2020.02.005"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-67101-7"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-2252-3"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0210276"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2007.07.011"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-94360-9"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.3892\/or.2014.3587"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0002339"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-66580-y"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2020.107972"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.6.4283"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2022.12821"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1051\/medsci\/200723167"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2022.155376"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0000000000001139"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1126\/science.1087262"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.3390\/cells11091502"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.654684"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21217831"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1080\/14712598.2021.1862791"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.issn.0253-2727.2021.11.009"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-21-0407"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15123136"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.18240\/ijo.2019.11.15"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.14-15168"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0145323"}],"container-title":["Ophthalmic 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