{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T07:15:00Z","timestamp":1789715700283,"version":"4.0.1"},"reference-count":77,"publisher":"American Society for Clinical Investigation","issue":"22","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81371022,81570860,81870665"],"award-info":[{"award-number":["81371022,81570860,81870665"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,11,14]]},"abstract":"<jats:p>\n                    Von Hippel\u2013Lindau (Vhl) protein inhibits hypoxia-inducible factor (Hif), yet its deletion in murine retina does not cause the extensive angiogenesis expected with Hif induction. The mechanism is unclear. Here we show that retinoblastoma tumor suppressor (Rb1) constrains expression of Hif target genes in the\n                    <jats:italic>\n                      Vhl\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    retina. Deleting\n                    <jats:italic>Rb1<\/jats:italic>\n                    induced extensive retinal neovascularization and autophagic ablation of photoreceptors in the\n                    <jats:italic>\n                      Vhl\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    retina. RNA-sequencing, ChIP, and reporter assays showed Rb1 recruitment to and repression of certain Hif target genes. Activating Rb1 by deleting cyclin D1 induced a partial defect in the retinal superficial vascular plexus. Unexpectedly, removing\n                    <jats:italic>Vhl<\/jats:italic>\n                    suppressed retinoblastoma formation in murine\n                    <jats:italic>Rb1\/Rbl1<\/jats:italic>\n                    \u2013deficient retina but generated subretinal vascular growths resembling retinal angiomatous proliferation (RAP) and retinal capillary hemangioblastoma (RCH). Most stromal cells in the RAP\/RCH\u2013like lesions were Sox9\n                    <jats:sup>+<\/jats:sup>\n                    , suggesting a M\u00fcller glia origin, and expressed Lgals3, a marker of human brain hemangioblastoma. Thus, the Rb family limit Hif target gene expression in the\n                    <jats:italic>\n                      Vhl\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    retina, and removing this inhibitory signal generates new models for RAP and RCH.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.127889","type":"journal-article","created":{"date-parts":[[2019,10,15]],"date-time":"2019-10-15T12:42:44Z","timestamp":1571143364000},"source":"Crossref","is-referenced-by-count":24,"title":["Rb1\/Rbl1\/Vhl loss induces mouse subretinal angiomatous proliferation and hemangioblastoma"],"prefix":"10.1172","volume":"4","author":[{"given":"Ran","family":"Wei","sequence":"first","affiliation":[{"name":"Research Laboratory of Ophthalmology and Vision Sciences, State Key Laboratory of Biotherapy, and"},{"name":"Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, 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