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Cellular prion protein (PrP\n                    <jats:sup>C<\/jats:sup>\n                    ), expressed in several neurovascular unit (NVU) cell types, regulates neuronal and astrocytic differentiation through laminin binding, yet its role in angiogenesis remains understudied. Here, we investigated its function in retinal vascular development. In PrP\n                    <jats:sup>C<\/jats:sup>\n                    knockout mice, the superficial retinal plexus exhibited increased tip cell density and branching, accompanied by microglial morphofunctional alterations and reduced\n                    <jats:italic>Vegf-c<\/jats:italic>\n                    expression, features consistent with impaired vascular stability. Conditioned media from PrP\n                    <jats:sup>C<\/jats:sup>\n                    knockout microglia was sufficient to increase endothelial instability in vitro, indicating that altered microglial signalling can modulate vascular phenotype. Moreover, Laminin 411 \/ 511 isoforms and Collagen IV showed decreased expression in the retinal vascular basement membrane, supporting altered basement membrane composition. At later developmental stages, absence of PrP\n                    <jats:sup>C<\/jats:sup>\n                    led to increased vertical sprouting into deeper retinal layers, resulting in transient hypervascularization of the deep plexus and defective laminin deposition across all vascular layers. These changes were accompanied by altered ZO-1 distribution and disrupted retinal layer organization, as indicated by reduced inter-plexus distance. Collectively, our findings identify PrP\n                    <jats:sup>C<\/jats:sup>\n                    as regulator of sprouting angiogenesis and vascular stabilization in the developing retina. The data support a model in which PrP\n                    <jats:sup>C<\/jats:sup>\n                    modulates neurovascular interactions, through both microglia-dependent and endothelial-intrinsic mechanisms, although the relative contribution of these components remains to be determined.\n                  <\/jats:p>","DOI":"10.1007\/s11064-026-04867-8","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T07:17:49Z","timestamp":1787728669000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cellular Prion Protein as a Novel Regulator of Vascular Plexus Stability During Retinal Angiogenesis"],"prefix":"10.1007","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4026-5586","authenticated-orcid":false,"given":"B\u00e1rbara Gomes","family":"da Rosa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7499-2765","authenticated-orcid":false,"given":"Felipe","family":"Leser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0196-9361","authenticated-orcid":false,"given":"Marco Aur\u00e9lio","family":"Alves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6891-9529","authenticated-orcid":false,"given":"Eliel","family":"de Souza Leite","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4492-8365","authenticated-orcid":false,"given":"Celina","family":"Garcia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3318-4697","authenticated-orcid":false,"given":"Luiz Henrique Medeiros","family":"Geraldo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7645-9086","authenticated-orcid":false,"given":"Rackele Ferreira","family":"do Amaral","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3393-5326","authenticated-orcid":false,"given":"Catarina","family":"Freitas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0799-9235","authenticated-orcid":false,"given":"Flavia Regina Souza","family":"Lima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"issue":"10","key":"4867_CR1","doi-asserted-by":"publisher","first-page":"1675","DOI":"10.1007\/s00018-013-1277-5","volume":"70","author":"C Ruhrberg","year":"2013","unstructured":"Ruhrberg C, Bautch VL (2013) Neurovascular development and links to disease. 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