{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T06:24:14Z","timestamp":1772173454790,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1012799","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000}}],"reference-count":67,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T00:00:00Z","timestamp":1757548800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100020581","name":"Fondazione AIRC per la ricerca sul cancro ETS","doi-asserted-by":"publisher","award":["IG 2019 ID: 23825"],"award-info":[{"award-number":["IG 2019 ID: 23825"]}],"id":[{"id":"10.13039\/100020581","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Retinal Hemangioblastoma (RH) is the most frequent manifestation of the von Hippel-Lindau syndrome (VHL), a rare disease associated with the germline mutation of the von Hippel-Lindau protein (pVHL). An emblematic feature of RH is the high vascularity, which is explained by the overexpression of angiogenic factors (AFs) arising from the pVHL impairment. The introduction of Optical Coherence Tomography Angiography (OCTA) allowed observing this feature with exceptional detail. Here, we combine OCTA images and a mechanistic model to investigate tumor growth and vascular development in a patient-specific way. We derived our model from the agreed pathology for RH and focused on the earliest stages of tumor-induced angiogenesis. Our simulations closely resemble the medical images, supporting the capability of our model to simulate vascular patterning in actual patients. Our results also suggest that angiogenesis in RH occurs upon reaching a critical dimension (around 200 \u03bcm), followed by the rapid formation of stable vascular networks. These findings open a new perspective on the crucial role of time in antiangiogenic therapy in RH, which has resulted in ineffective control. Indeed, it might be that when RH is diagnosed, angiogenesis is already too advanced to be effectively targeted with any effective means. Moreover, our simulations suggest that vascularization in RH is not a continuous process but an inconstant development with long, stable phases and rapid episodes of vascular sprouting.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1012799","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T17:44:40Z","timestamp":1757612680000},"page":"e1012799","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mathematical modeling and simulation of tumor-induced angiogenesis in retinal hemangioblastoma"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7152-5512","authenticated-orcid":true,"given":"Franco","family":"Pradelli","sequence":"first","affiliation":[]},{"given":"Giovanni","family":"Minervini","sequence":"additional","affiliation":[]},{"given":"Pradeep","family":"Venkatesh","sequence":"additional","affiliation":[]},{"given":"Shorya","family":"Azad","sequence":"additional","affiliation":[]},{"given":"Hector","family":"Gomez","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4525-7793","authenticated-orcid":true,"given":"Silvio C. 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