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In contrast, LRG1 is not involved in developmental angiogenesis. Here, we investigated the vasculopathic properties of LRG1 by examining its effect on developing retinal blood vessels. By injecting recombinant protein or an expression vector into the mouse retina during vascular development, we showed that exogenous LRG1 reduces pericyte coverage and NG2 expression. It leads to diminished collagen IV sheathing, fewer adhesion and gap junctions, and reduced vessel calibre and vascular density. Moreover, in mouse retinae containing exogenous LRG1, the developing blood\u2013retinal barrier remains more permeable with significantly higher numbers of transcytotic vesicles present in microvascular endothelial cells. These results reveal that exogeneous LRG1 is sufficient to interfere with the maturation of developing retinal vessels and drive vessel development towards a dysfunctional phenotype. These observations deliver further evidence that LRG1 is an angiopathic factor and highlight the therapeutic potential of blocking LRG1 in diseases characterized by pathogenic angiogenesis or vascular remodelling.<\/jats:p>","DOI":"10.3390\/cells14080593","type":"journal-article","created":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T09:06:51Z","timestamp":1744621611000},"page":"593","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["LRG1 Alters Pericyte Phenotype and Compromises Vascular Maturation"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5123-1760","authenticated-orcid":false,"given":"Alexandra E.","family":"Hoeh","sequence":"first","affiliation":[{"name":"Institute of Ophthalmology, University College London, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jui-Hsien","family":"Chang","sequence":"additional","affiliation":[{"name":"Institute of Ophthalmology, University College London, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4835-6335","authenticated-orcid":false,"given":"Ronja S.","family":"Mueller","sequence":"additional","affiliation":[{"name":"Institute of Ophthalmology, University College London, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Basche","sequence":"additional","affiliation":[{"name":"Institute of Ophthalmology, University College London, London EC1V 9EL, UK"},{"name":"Ocular Cell and Gene Therapy Group, Centre for Gene Therapy and Regenerative Medicine, King\u2019s College London, London SE1 9RT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5517-6068","authenticated-orcid":false,"given":"Alessandro","family":"Fantin","sequence":"additional","affiliation":[{"name":"Department of Biosciences, University of Milan, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasios","family":"Sepetis","sequence":"additional","affiliation":[{"name":"Institute of Ophthalmology, University College London, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6163-4590","authenticated-orcid":false,"given":"Giulia","family":"De Rossi","sequence":"additional","affiliation":[{"name":"Institute of Ophthalmology, University College London, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athina","family":"Dritsoula","sequence":"additional","affiliation":[{"name":"Institute of Ophthalmology, University College London, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin R.","family":"Ali","sequence":"additional","affiliation":[{"name":"Institute of Ophthalmology, University College London, London EC1V 9EL, UK"},{"name":"Ocular Cell and Gene Therapy Group, Centre for Gene Therapy and Regenerative Medicine, King\u2019s College London, London SE1 9RT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7660-5802","authenticated-orcid":false,"given":"Patric","family":"Turowski","sequence":"additional","affiliation":[{"name":"Institute of Ophthalmology, University College London, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen E.","family":"Moss","sequence":"additional","affiliation":[{"name":"Institute of Ophthalmology, University College London, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4496-2984","authenticated-orcid":false,"given":"John","family":"Greenwood","sequence":"additional","affiliation":[{"name":"Institute of Ophthalmology, University College London, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1146\/annurev-cellbio-092910-154002","article-title":"Developmental and pathological angiogenesis","volume":"27","author":"Chung","year":"2011","journal-title":"Annu. 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