{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:59:14Z","timestamp":1787018354689,"version":"build-2736575974"},"reference-count":95,"publisher":"American Society for Clinical Investigation","issue":"18","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,9,20]]},"abstract":"<jats:p>\n                    Age-related macular degeneration (AMD), a progressive chronic disease of the central retina, is associated with aging and is a leading cause of blindness worldwide. Here, we demonstrate that leukotriene B\n                    <jats:sub>4<\/jats:sub>\n                    (LTB\n                    <jats:sub>4<\/jats:sub>\n                    ) receptor 1 (BLT1) promotes laser-induced choroidal neovascularization (CNV) in a mouse model for wet-type AMD. CNV was significantly less in BLT1-deficient (BLT1-KO) mice compared with BLT1-WT controls. Expression of several proangiogenic and profibrotic factors was lower in BLT1-KO eyes than in BLT1-WT eyes. LTB\n                    <jats:sub>4<\/jats:sub>\n                    production in the eyes was substantially increased in the early phase after laser injury. BLT1 was highly expressed in M2 macrophages in vitro and in vivo, and ocular BLT1\n                    <jats:sup>+<\/jats:sup>\n                    M2 macrophages were increased in the aged eyes after laser injury. Furthermore, M2 macrophages were rapidly attracted by LTB\n                    <jats:sub>4<\/jats:sub>\n                    and subsequently produced VEGF-A\u2013 through BLT1-mediated signaling. Consequently, intravitreal injection of M2 macrophages augmented CNV formation, which was attenuated by BLT1 deficiency. Thus, laser-induced injury to the retina triggered LTB\n                    <jats:sub>4<\/jats:sub>\n                    production and attracted M2 macrophages via BLT1, leading to development of CNV. A selective BLT1 antagonist (CP105696) and 3 LTB\n                    <jats:sub>4<\/jats:sub>\n                    inhibitors (zileuton, MK-886, and bestatin) reduced CNV in a dose-dependent manner. CP105696 also inhibited the accumulation of BLT1\n                    <jats:sup>+<\/jats:sup>\n                    M2 macrophages in the laser-injured eyes of aged mice. Together, these results indicate that the LTB\n                    <jats:sub>4<\/jats:sub>\n                    -BLT1 axis is a potentially novel therapeutic target for CNV of wet-type AMD.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.96902","type":"journal-article","created":{"date-parts":[[2018,9,19]],"date-time":"2018-09-19T11:01:59Z","timestamp":1537354919000},"source":"Crossref","is-referenced-by-count":40,"title":["Leukotriene B4 promotes neovascularization and macrophage recruitment in murine wet-type AMD models"],"prefix":"10.1172","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6699-6654","authenticated-orcid":true,"given":"Fumiyuki","family":"Sasaki","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Juntendo University School of Medicine, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoaki","family":"Koga","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Juntendo 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