{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:29:52Z","timestamp":1787016592074,"version":"build-2736575974"},"reference-count":90,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"774","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2024,11,20]]},"abstract":"<jats:p>\n                    Roundabout (ROBO) 1 and 2 are transmembrane receptors that bind secreted SLIT ligands through their extracellular domains (ECDs) and signal through their cytoplasmic domains to modulate the cytoskeleton and regulate cell migration, adhesion, and proliferation. SLIT-ROBO signaling regulates pathological ocular neovascularization, which is a major cause of vision loss worldwide, but pharmacological tools to prevent SLIT-ROBO signaling are lacking. Here, we developed human monoclonal antibodies (mAbs) against the ROBO1 and ROBO2 ECDs. One antibody that inhibited in vitro SLIT2 signaling through ROBO1 and ROBO2 (anti-ROBO1\/2) also reduced ocular neovascularization in oxygen-induced retinopathy (OIR) and laser-induced corneal neovascularization (CNV) mouse models in vivo. Single-cell RNA sequencing of OIR retinas revealed that antibody treatment affected several cell types relevant to physiological and pathological angiogenesis, including endothelial cells, pericytes, and a heterogeneous population of myeloid cells. mAb treatment improved blood-retina barrier integrity and prevented pathological pericyte activation in OIR. SLIT-ROBO signaling inhibition prevented pathological activation of myeloid cells and increased neuroprotective myeloid populations normally seen in the developing retina. Microglia\/infiltrating macrophage\u2013specific ablation of\n                    <jats:italic>Robo1<\/jats:italic>\n                    and\n                    <jats:italic>Robo2<\/jats:italic>\n                    or knockout of the downstream effector phosphatidylinositol 3-kinase (\n                    <jats:italic>Pik3cg<\/jats:italic>\n                    ) encoding PI3K\u03b3 in both OIR and CNV models phenocopied anti-ROBO1\/2 treatment, further demonstrating the key role of myeloid cells as drivers of ocular neovascular diseases. ROBO1\/2 blocking antibodies may thus provide a promising strategy to combat inflammation in blinding eye diseases.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.adn8388","type":"journal-article","created":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T13:58:11Z","timestamp":1732111091000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":14,"title":["Monoclonal antibodies that block Roundabout 1 and 2 signaling target pathological ocular neovascularization through myeloid cells"],"prefix":"10.1126","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3318-4697","authenticated-orcid":true,"given":"Luiz Henrique","family":"Geraldo","sequence":"first","affiliation":[{"name":"Cardiovascular Research Center, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510, USA."},{"name":"Department of Cellular and Molecular Physiology, Yale University School of Medicine, New 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Immunobiology, Yale School of Medicine, New Haven, CT 06510, USA."},{"name":"Department of Ophthalmology and Visual Sciences, Yale University School of Medicine, New Haven, CT 06510, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2363-6047","authenticated-orcid":true,"given":"Mark E.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Center of Molecular and Cellular Oncology, Yale Cancer Center, Yale School of Medicine, New Haven, CT 06510, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3397-0292","authenticated-orcid":true,"given":"Jean-Leon","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA."},{"name":"Paris Brain Institute, Universit\u00e9 Pierre et Marie Curie Paris 06 UMRS1127, Sorbonne Universit\u00e9, F-75013 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachdev S.","family":"Sidhu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Waterloo, Kitchener, Ontario N2G 1C5, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5563-210X","authenticated-orcid":true,"given":"Anne","family":"Eichmann","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Center, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510, USA."},{"name":"Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06510, USA."},{"name":"Universit\u00e9 de Paris, INSERM, PARCC, F-75015 Paris, 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