{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T23:54:34Z","timestamp":1790553274764,"version":"4.1.0"},"reference-count":29,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,18]],"date-time":"2021-08-18T00:00:00Z","timestamp":1629244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"I.Ri.Fo.R (Istituto per la Ricerca, la Formazione e la Riabilitazione Onlus)","award":["number prot.2747-08\/08\/2019"],"award-info":[{"award-number":["number prot.2747-08\/08\/2019"]}]},{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["\u201cDipartimento di Eccellenza\u201d 2018\u20132022"],"award-info":[{"award-number":["\u201cDipartimento di Eccellenza\u201d 2018\u20132022"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["Investigator award 206413\/B\/17\/Z"],"award-info":[{"award-number":["Investigator award 206413\/B\/17\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Leucine-rich a-2-glycoprotein 1 (LRG1) is a candidate therapeutic target for treating the neovascular form of age-related macular degeneration (nvAMD). In this study we examined the expression of LRG1 in eyes of nvAMD patients. Choroidal neovascular membranes (CNVMs) from patients who underwent submacular surgery for retinal pigment epithelium\u2013choroid graft transplantation were collected from 5 nvAMD patients without any prior intravitreal anti-VEGF injection, and from six patients who received intravitreal anti-VEGF injections before surgery. As controls free of nvAMD, retina sections were obtained from the eyes resected from a patient with lacrimal sac tumor and from a patient with neuroblastoma. CNVMs were immunostained for CD34, LRG1, and \u03b1-smooth muscle actin (\u03b1-SMA). Aqueous humor samples were collected from 58 untreated-na\u00efve nvAMD patients prior to the intravitreal injection of anti-VEGF and 51 age-matched cataract control patients, and LRG1 concentration was measured by ELISA. The level of LRG1 immunostaining is frequently high in both the endothelial cells of the blood vessels, and myofibroblasts in the surrounding tissue of CNVMs of treatment-na\u00efve nvAMD patients. Furthermore, the average concentration of LRG1 was significantly higher in the aqueous humor of nvAMD patients than in controls. These observations provide a strong experimental basis and scientific rationale for the progression of a therapeutic anti-LRG1 monoclonal antibody into clinical trials with patients with nvAMD.<\/jats:p>","DOI":"10.3390\/ijms22168879","type":"journal-article","created":{"date-parts":[[2021,8,18]],"date-time":"2021-08-18T10:54:35Z","timestamp":1629284075000},"page":"8879","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["LRG1 Expression Is Elevated in the Eyes of Patients with Neovascular Age-Related Macular Degeneration"],"prefix":"10.3390","volume":"22","author":[{"given":"Lucia","family":"Mundo","sequence":"first","affiliation":[{"name":"Section of Pathology, Department of Medical Biotechnology, University of Siena, 53100 Siena, Italy"},{"name":"Health Research Institute, University of Limerick, V94 T9PX Limerick, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gian","family":"Tosi","sequence":"additional","affiliation":[{"name":"Ophthalmology Unit, Department of Medicine, Surgery and Neuroscience, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Lazzi","sequence":"additional","affiliation":[{"name":"Section of Pathology, Department of Medical Biotechnology, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grazia","family":"Pertile","sequence":"additional","affiliation":[{"name":"IRCCS Sacro Cuore Don Calabria Hospital, 37024 Negrar, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Parolini","sequence":"additional","affiliation":[{"name":"Vitroretinal Unit, Sant\u2019Anna Hospital, 25127 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Neri","sequence":"additional","affiliation":[{"name":"Ophthalmology Unit, Department of Medicine, Surgery and Neuroscience, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3983-0381","authenticated-orcid":false,"given":"Matteo","family":"Posarelli","sequence":"additional","affiliation":[{"name":"Ophthalmology Unit, Department of Medicine, Surgery and Neuroscience, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"De Benedetto","sequence":"additional","affiliation":[{"name":"Ophthalmology Unit, Department of Medicine, Surgery and Neuroscience, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7477-2263","authenticated-orcid":false,"given":"Tommaso","family":"Bacci","sequence":"additional","affiliation":[{"name":"Ophthalmology Unit, Department of Medicine, Surgery and Neuroscience, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ennio","family":"Silvestri","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via A. Moro, 2, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Siciliano","sequence":"additional","affiliation":[{"name":"Section of Pathology, Department of Medical Biotechnology, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Barbera","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via A. Moro, 2, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Orlandini","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via A. Moro, 2, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4496-2984","authenticated-orcid":false,"given":"John","family":"Greenwood","sequence":"additional","affiliation":[{"name":"UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Moss","sequence":"additional","affiliation":[{"name":"UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1967-9554","authenticated-orcid":false,"given":"Federico","family":"Galvagni","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via A. Moro, 2, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Arruabarrena, C., Toro, M., Onen, M., Malyugin, B., Rejdak, R., Tognetto, D., Zweifel, S., Giglio, R., and Teus, M. (2021). Impact on Visual Acuity in Neovascular Age Related Macular Degeneration (nAMD) in Europe Due to COVID-19 Pandemic Lockdown. J. Clin. Med., 10.","DOI":"10.3390\/jcm10153281"},{"key":"ref_2","first-page":"1","article-title":"Age-related macular degeneration","volume":"7","author":"Fleckenstein","year":"2021","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1097\/ICU.0000000000000657","article-title":"Age-related macular degeneration therapy: A review","volume":"31","author":"Ammar","year":"2020","journal-title":"Curr. Opin. 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