{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:21:32Z","timestamp":1790806892746,"version":"4.1.0"},"reference-count":63,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    This study investigated the one-year real-world clinical outcomes of intravitreal faricimab (IVF) in treatment-na\u00efve neovascular age-related macular degeneration (nAMD) and its association with aqueous humor cytokine profiles. Thirty-four eyes of 32 nAMD patients, who received initial IVF at Jichi Medical University were included. These eyes showed significant improvements in central retinal subfield thickness (CST), central choroidal thickness (CCT), and best-corrected visual acuity (BCVA) one year post-IVF (all\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.01). Among 24 measurable cytokines, only VEGF-A was significantly higher in eyes with a dry macula at week 16 (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.0030). Three cytokines were significantly higher in eyes with longer injection interval. Higher levels of galectin-1 and VCAM-1, and lower levels of P-selectin, were correlated with greater CST reduction (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.020, 0.0061, and 0.012, respectively). Conversely, five cytokines including Ang-1 were correlated with greater BCVA improvement (all\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.05). In conclusion, an anatomical perspective faricimab demonstrated anatomical efficacy for VEGF-driven nAMD in the loading phase, while multiple cytokines associated with vascular instability or fibrosis appear to contribute to its durability. Notably, Ang-1 may be linked to visual improvement, suggesting that the neurotrophic effects of Ang-1 could be enhanced by Ang-2 inhibition.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-28911-9","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T13:43:40Z","timestamp":1767015820000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["One year outcomes of intravitreal faricimab for treatment Na\u00efve neovascular AMD and associations with baseline aqueous humor cytokines"],"prefix":"10.1038","volume":"15","author":[{"given":"Satoru","family":"Inoda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidenori","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuto","family":"Hashimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hana","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironori","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Takayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shouma","family":"Tsuchiya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daizo","family":"Matsumoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidetoshi","family":"Kawashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshikatsu","family":"Kaburaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuo","family":"Yanagi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,29]]},"reference":[{"key":"28911_CR1","doi-asserted-by":"publisher","unstructured":"Takahashi, K. et al. Efficacy, durability, and safety of faricimab in patients from Asian countries with neovascular age-related macular degeneration: 1-Year subgroup analysis of the TENAYA and LUCERNE trials. Graefes Arch. Clin. Exp. Ophthalmol. 1\u201313. https:\/\/doi.org\/10.1007\/s00417-023-06071-8 (2023).","DOI":"10.1007\/s00417-023-06071-8"},{"key":"28911_CR2","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1007\/s10384-023-00985-w","volume":"67","author":"R Mori","year":"2023","unstructured":"Mori, R. et al. Efficacy, durability, and safety of faricimab up to every 16 weeks in patients with neovascular age-related macular degeneration: 1-year results from the Japan subgroup of the phase 3 TENAYA trial. Jpn J. Ophthalmol. 67, 301\u2013310. https:\/\/doi.org\/10.1007\/s10384-023-00985-w (2023).","journal-title":"Jpn J. Ophthalmol."},{"key":"28911_CR3","doi-asserted-by":"publisher","first-page":"8747","DOI":"10.1038\/s41598-023-35759-4","volume":"13","author":"R Mukai","year":"2023","unstructured":"Mukai, R. et al. Three-month outcomes of faricimab loading therapy for wet age-related macular degeneration in Japan. Sci. Rep. 13, 8747. https:\/\/doi.org\/10.1038\/s41598-023-35759-4 (2023).","journal-title":"Sci. Rep."},{"key":"28911_CR4","doi-asserted-by":"publisher","DOI":"10.1007\/s00417-023-06116-y","author":"H Matsumoto","year":"2023","unstructured":"Matsumoto, H., Hoshino, J., Nakamura, K., Nagashima, T. & Akiyama, H. Short-term outcomes of intravitreal faricimab for treatment-naive neovascular age-related macular degeneration. Graefes Arch. Clin. Exp. Ophthalmol. https:\/\/doi.org\/10.1007\/s00417-023-06116-y (2023).","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"28911_CR5","doi-asserted-by":"publisher","DOI":"10.1007\/s40123-023-00779-w","author":"S Inoda","year":"2023","unstructured":"Inoda, S. et al. Visual and anatomical outcomes after initial intravitreal faricimab injection for neovascular Age-Related macular degeneration in patients with prior treatment history. Ophthalmol. Ther. https:\/\/doi.org\/10.1007\/s40123-023-00779-w (2023).","journal-title":"Ophthalmol. Ther."},{"key":"28911_CR6","doi-asserted-by":"publisher","first-page":"9087","DOI":"10.1038\/s41598-024-59894-8","volume":"14","author":"H Takahashi","year":"2024","unstructured":"Takahashi, H. et al. One-year visual and anatomical outcomes of intravitreal faricimab injection for neovascular age-related macular degeneration after prior Brolucizumab treatment. Sci. Rep. 14, 9087. https:\/\/doi.org\/10.1038\/s41598-024-59894-8 (2024).","journal-title":"Sci. Rep."},{"key":"28911_CR7","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1007\/s00417-021-05445-0","volume":"260","author":"S Inoda","year":"2022","unstructured":"Inoda, S. et al. Cytokine profiles of macular neovascularization in the elderly based on a classification from a pachychoroid\/drusen perspective. Graefes Arch. Clin. Exp. Ophthalmol. 260, 747\u2013758. https:\/\/doi.org\/10.1007\/s00417-021-05445-0 (2022).","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"28911_CR8","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1097\/iae.0000000000003699","volume":"43","author":"D Eichenbaum","year":"2023","unstructured":"Eichenbaum, D. et al. IMPACT OF RETINAL FLUID-FREE MONTHS ON OUTCOMES IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A treatment agnostic analysis of the HAWK and HARRIER studies. Retina 43, 632\u2013640. https:\/\/doi.org\/10.1097\/iae.0000000000003699 (2023).","journal-title":"Retina"},{"key":"28911_CR9","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1016\/j.ophtha.2018.11.025","volume":"126","author":"RH Guymer","year":"2019","unstructured":"Guymer, R. H. et al. Tolerating subretinal fluid in neovascular Age-Related macular degeneration treated with Ranibizumab using a Treat-and-Extend regimen: FLUID study 24-Month results. Ophthalmology 126, 723\u2013734. https:\/\/doi.org\/10.1016\/j.ophtha.2018.11.025 (2019).","journal-title":"Ophthalmology"},{"key":"28911_CR10","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1016\/j.ophtha.2018.08.035","volume":"126","author":"GJ Jaffe","year":"2019","unstructured":"Jaffe, G. J. et al. Macular morphology and visual acuity in year five of the comparison of Age-related macular degeneration treatments trials. Ophthalmology 126, 252\u2013260. https:\/\/doi.org\/10.1016\/j.ophtha.2018.08.035 (2019).","journal-title":"Ophthalmology"},{"key":"28911_CR11","doi-asserted-by":"publisher","first-page":"2983","DOI":"10.1038\/s41433-020-01354-4","volume":"35","author":"U Chakravarthy","year":"2021","unstructured":"Chakravarthy, U. et al. Impact of macular fluid volume fluctuations on visual acuity during anti-VEGF therapy in eyes with nAMD. Eye (Lond). 35, 2983\u20132990. https:\/\/doi.org\/10.1038\/s41433-020-01354-4 (2021).","journal-title":"Eye (Lond)"},{"key":"28911_CR12","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1007\/s10384-023-01040-4","volume":"68","author":"H Matsumoto","year":"2024","unstructured":"Matsumoto, H., Hoshino, J., Nakamura, K. & Akiyama, H. One-year results of treat-and-extend regimen with intravitreal faricimab for treatment-na\u00efve neovascular age-related macular degeneration. Jpn J. Ophthalmol. 68, 83\u201390. https:\/\/doi.org\/10.1007\/s10384-023-01040-4 (2024).","journal-title":"Jpn J. Ophthalmol."},{"key":"28911_CR13","doi-asserted-by":"publisher","first-page":"3249","DOI":"10.1038\/s41598-023-30146-5","volume":"13","author":"H Matsumoto","year":"2023","unstructured":"Matsumoto, H., Hoshino, J., Nakamura, K. & Akiyama, H. Two-year outcomes of treat-and-extend regimen with intravitreal Brolucizumab for treatment-na\u00efve neovascular age-related macular degeneration with type 1 macular neovascularization. Sci. Rep. 13, 3249. https:\/\/doi.org\/10.1038\/s41598-023-30146-5 (2023).","journal-title":"Sci. Rep."},{"key":"28911_CR14","doi-asserted-by":"publisher","first-page":"3637","DOI":"10.1007\/s00417-021-05293-y","volume":"259","author":"M Ohji","year":"2021","unstructured":"Ohji, M. et al. Relationship between retinal fluid and visual acuity in patients with exudative age-related macular degeneration treated with intravitreal Aflibercept using a treat-and-extend regimen: subgroup and post-hoc analyses from the ALTAIR study. Graefes Arch. Clin. Exp. Ophthalmol. 259, 3637\u20133647. https:\/\/doi.org\/10.1007\/s00417-021-05293-y (2021).","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"28911_CR15","doi-asserted-by":"publisher","unstructured":"Ferro Desideri, L., Traverso, C. E., Nicol\u00f2, M. & Munk, M. R. Faricimab for the treatment of diabetic macular edema and neovascular Age-Related macular degeneration. Pharmaceutics 15 https:\/\/doi.org\/10.3390\/pharmaceutics15051413 (2023).","DOI":"10.3390\/pharmaceutics15051413"},{"key":"28911_CR16","doi-asserted-by":"publisher","first-page":"1991","DOI":"10.1172\/jci58832","volume":"122","author":"M Felcht","year":"2012","unstructured":"Felcht, M. et al. Angiopoietin-2 differentially regulates angiogenesis through TIE2 and integrin signaling. J. Clin. Invest. 122, 1991\u20132005. https:\/\/doi.org\/10.1172\/jci58832 (2012).","journal-title":"J. Clin. Invest."},{"key":"28911_CR17","doi-asserted-by":"publisher","first-page":"783178","DOI":"10.3389\/fmed.2021.783178","volume":"8","author":"C Liu","year":"2021","unstructured":"Liu, C. et al. Comparison of intraocular cytokine levels of choroidal neovascularization secondary to different retinopathies. Front. Med. (Lausanne). 8, 783178. https:\/\/doi.org\/10.3389\/fmed.2021.783178 (2021).","journal-title":"Front. Med. (Lausanne)"},{"key":"28911_CR18","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1159\/000365487","volume":"53","author":"Y Sakurada","year":"2015","unstructured":"Sakurada, Y. et al. Aqueous humor cytokine levels in patients with polypoidal choroidal vasculopathy and neovascular age-related macular degeneration. Ophthalmic Res. 53, 2\u20137. https:\/\/doi.org\/10.1159\/000365487 (2015).","journal-title":"Ophthalmic Res."},{"key":"28911_CR19","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1136\/bjophthalmol-2017-310284","volume":"102","author":"S Sakamoto","year":"2018","unstructured":"Sakamoto, S. et al. Changes in multiple cytokine concentrations in the aqueous humour of neovascular age-related macular degeneration after 2 months of Ranibizumab therapy. Br. J. Ophthalmol. 102, 448\u2013454. https:\/\/doi.org\/10.1136\/bjophthalmol-2017-310284 (2018).","journal-title":"Br. J. Ophthalmol."},{"key":"28911_CR20","doi-asserted-by":"publisher","first-page":"1968","DOI":"10.1111\/febs.16272","volume":"289","author":"TT Wei","year":"2022","unstructured":"Wei, T. T. et al. Interferon-\u03b3 induces retinal pigment epithelial cell ferroptosis by a JAK1-2\/STAT1\/SLC7A11 signaling pathway in Age-related macular degeneration. Febs j. 289, 1968\u20131983. https:\/\/doi.org\/10.1111\/febs.16272 (2022).","journal-title":"Febs j."},{"key":"28911_CR21","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1159\/000484907","volume":"44","author":"J Chen","year":"2017","unstructured":"Chen, J., Wang, W. & Li, Q. Increased Th1\/Th17 responses contribute to Low-Grade inflammation in Age-Related macular degeneration. Cell. Physiol. Biochem. 44, 357\u2013367. https:\/\/doi.org\/10.1159\/000484907 (2017).","journal-title":"Cell. Physiol. Biochem."},{"key":"28911_CR22","first-page":"1076","volume":"112","author":"K Takahashi","year":"2008","unstructured":"Takahashi, K., Ishibashi, T., Ogur, Y. & Yuzawa, M. [Classification and diagnostic criteria of age-related macular degeneration]. Nippon Ganka Gakkai Zasshi. 112, 1076\u20131084 (2008).","journal-title":"Nippon Ganka Gakkai Zasshi"},{"key":"28911_CR23","doi-asserted-by":"publisher","first-page":"3815","DOI":"10.1007\/s00417-024-06577-9","volume":"262","author":"H Yoshida","year":"2024","unstructured":"Yoshida, H. et al. Two-year outcomes of intravitreal Brolucizumab for neovascular age-related macular degeneration: treat, extend, and stop-protocol. Graefes Arch. Clin. Exp. Ophthalmol. 262, 3815\u20133823. https:\/\/doi.org\/10.1007\/s00417-024-06577-9 (2024).","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"28911_CR24","doi-asserted-by":"publisher","first-page":"e88324","DOI":"10.1371\/journal.pone.0088324","volume":"9","author":"ZY Wang","year":"2014","unstructured":"Wang, Z. Y. et al. Systematic review and meta-analysis of the association between complement factor H I62V polymorphism and risk of polypoidal choroidal vasculopathy in Asian populations. PLoS One. 9, e88324. https:\/\/doi.org\/10.1371\/journal.pone.0088324 (2014).","journal-title":"PLoS One"},{"key":"28911_CR25","doi-asserted-by":"publisher","first-page":"1491","DOI":"10.1038\/s41598-018-19473-0","volume":"8","author":"M Yamashita","year":"2018","unstructured":"Yamashita, M. et al. Intravitreal injection of aflibercept, an anti-VEGF antagonist, down-regulates plasma von Willebrand factor in patients with age-related macular degeneration. Sci. Rep. 8, 1491. https:\/\/doi.org\/10.1038\/s41598-018-19473-0 (2018).","journal-title":"Sci. Rep."},{"key":"28911_CR26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/iae.0000000000000774","volume":"36","author":"C Balaratnasingam","year":"2016","unstructured":"Balaratnasingam, C. et al. Polypoidal choroidal vasculopathy: A distinct disease or manifestation of many? Retina 36, 1\u20138. https:\/\/doi.org\/10.1097\/iae.0000000000000774 (2016).","journal-title":"Retina"},{"key":"28911_CR27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/iae.0000000000000331","volume":"35","author":"CE Pang","year":"2015","unstructured":"Pang, C. E. & Freund, K. B. Pachychoroid neovasculopathy. Retina 35, 1\u20139. https:\/\/doi.org\/10.1097\/iae.0000000000000331 (2015).","journal-title":"Retina"},{"key":"28911_CR28","doi-asserted-by":"publisher","first-page":"16204","DOI":"10.1038\/srep16204","volume":"5","author":"M Miyake","year":"2015","unstructured":"Miyake, M. et al. Pachychoroid neovasculopathy and age-related macular degeneration. Sci. Rep. 5, 16204. https:\/\/doi.org\/10.1038\/srep16204 (2015).","journal-title":"Sci. Rep."},{"key":"28911_CR29","first-page":"2856","volume":"17","author":"SM Ecker","year":"2011","unstructured":"Ecker, S. M., Hines, J. C., Pfahler, S. M. & Glaser, B. M. Aqueous cytokine and growth factor levels do not reliably reflect those levels found in the vitreous. Mol. Vis. 17, 2856\u20132863 (2011).","journal-title":"Mol. Vis."},{"key":"28911_CR30","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1016\/S0140-6736(22)00010-1","volume":"399","author":"JS Heier","year":"2022","unstructured":"Heier, J. S. et al. Efficacy, durability, and safety of intravitreal faricimab up to every 16 weeks for neovascular age-related macular degeneration (TENAYA and LUCERNE): two randomised, double-masked, phase 3, non-inferiority trials. Lancet 399, 729\u2013740. https:\/\/doi.org\/10.1016\/S0140-6736(22)00010-1 (2022).","journal-title":"Lancet"},{"key":"28911_CR31","doi-asserted-by":"publisher","first-page":"11681","DOI":"10.1038\/s41598-024-62559-1","volume":"14","author":"R Mukai","year":"2024","unstructured":"Mukai, R. et al. One-year outcomes and safety assessment of faricimab in treatment-na\u00efve patients with neovascular age-related macular degeneration in Japan. Sci. Rep. 14, 11681. https:\/\/doi.org\/10.1038\/s41598-024-62559-1 (2024).","journal-title":"Sci. Rep."},{"key":"28911_CR32","doi-asserted-by":"publisher","first-page":"2323","DOI":"10.1007\/s40123-023-00768-z","volume":"12","author":"PJ Patel","year":"2023","unstructured":"Patel, P. J., Villavicencio, P. & Hanumunthadu, D. Systematic review of neovascular Age-Related macular degeneration disease activity criteria use to Shorten, maintain or extend treatment intervals with Anti-VEGF in clinical trials: implications for clinical practice. Ophthalmol. Ther. 12, 2323\u20132346. https:\/\/doi.org\/10.1007\/s40123-023-00768-z (2023).","journal-title":"Ophthalmol. Ther."},{"key":"28911_CR33","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1097\/apo.0000000000000445","volume":"10","author":"V Chaikitmongkol","year":"2021","unstructured":"Chaikitmongkol, V. et al. Treat-and-Extend regimens for the management of neovascular Age-related macular degeneration and polypoidal choroidal vasculopathy: consensus and recommendations from the Asia-Pacific Vitreo-retina society. Asia Pac. J. Ophthalmol. (Phila). 10, 507\u2013518. https:\/\/doi.org\/10.1097\/apo.0000000000000445 (2021).","journal-title":"Asia Pac. J. Ophthalmol. (Phila)"},{"key":"28911_CR34","doi-asserted-by":"publisher","first-page":"1010","DOI":"10.1097\/iae.0000000000002713","volume":"40","author":"DT Wong","year":"2020","unstructured":"Wong, D. T., Lambrou, G. N., Loewenstein, A., Pearce, I. & Okada, A. A. SUSPENDING TREATMENT OF NEOVASCULAR AGE-RELATED MACULAR DEGENERATION IN CASES OF FUTILITY. Retina 40, 1010\u20131020. https:\/\/doi.org\/10.1097\/iae.0000000000002713 (2020).","journal-title":"Retina"},{"key":"28911_CR35","doi-asserted-by":"publisher","first-page":"8195","DOI":"10.1038\/s41598-022-10578-1","volume":"12","author":"H Matsumoto","year":"2022","unstructured":"Matsumoto, H., Hoshino, J., Mukai, R., Nakamura, K. & Akiyama, H. One-year results of treat-and-extend regimen with intravitreal Brolucizumab for treatment-na\u00efve neovascular age-related macular degeneration with type 1 macular neovascularization. Sci. Rep. 12, 8195. https:\/\/doi.org\/10.1038\/s41598-022-10578-1 (2022).","journal-title":"Sci. Rep."},{"key":"28911_CR36","doi-asserted-by":"publisher","first-page":"31951","DOI":"10.1038\/s41598-024-83473-6","volume":"14","author":"R Nonogaki","year":"2024","unstructured":"Nonogaki, R. et al. Analysis of the aqueous humor before and after the administration of faricimab in patients with nAMD. Sci. Rep. 14, 31951. https:\/\/doi.org\/10.1038\/s41598-024-83473-6 (2024).","journal-title":"Sci. Rep."},{"key":"28911_CR37","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1002\/med.10001","volume":"22","author":"H Yusuf-Makagiansar","year":"2002","unstructured":"Yusuf-Makagiansar, H., Anderson, M. E., Yakovleva, T. V., Murray, J. S. & Siahaan, T. J. Inhibition of LFA-1\/ICAM-1 and VLA-4\/VCAM-1 as a therapeutic approach to inflammation and autoimmune diseases. Med. Res. Rev. 22, 146\u2013167. https:\/\/doi.org\/10.1002\/med.10001 (2002).","journal-title":"Med. Res. Rev."},{"key":"28911_CR38","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1002\/jlb.2mr0220-549r","volume":"108","author":"TM Bui","year":"2020","unstructured":"Bui, T. M., Wiesolek, H. L. & Sumagin, R. ICAM-1: A master regulator of cellular responses in inflammation, injury resolution, and tumorigenesis. J. Leukoc. Biol. 108, 787\u2013799. https:\/\/doi.org\/10.1002\/jlb.2mr0220-549r (2020).","journal-title":"J. Leukoc. Biol."},{"key":"28911_CR39","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1084\/jem.181.2.669","volume":"181","author":"K Ley","year":"1995","unstructured":"Ley, K. et al. Sequential contribution of L- and P-selectin to leukocyte rolling in vivo. J. Exp. Med. 181, 669\u2013675. https:\/\/doi.org\/10.1084\/jem.181.2.669 (1995).","journal-title":"J. Exp. Med."},{"key":"28911_CR40","doi-asserted-by":"publisher","first-page":"L533","DOI":"10.1152\/ajplung.1998.275.3.L533","volume":"275","author":"A Rahman","year":"1998","unstructured":"Rahman, A., Kefer, J., Bando, M., Niles, W. D. & Malik, A. B. E-selectin expression in human endothelial cells by TNF-alpha-induced oxidant generation and NF-kappaB activation. Am. J. Physiol. 275, L533\u2013544. https:\/\/doi.org\/10.1152\/ajplung.1998.275.3.L533 (1998).","journal-title":"Am. J. Physiol."},{"key":"28911_CR41","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1083\/jcb.112.4.749","volume":"112","author":"KD Patel","year":"1991","unstructured":"Patel, K. D., Zimmerman, G. A., Prescott, S. M., McEver, R. P. & McIntyre, T. M. Oxygen radicals induce human endothelial cells to express GMP-140 and bind neutrophils. J. Cell. Biol. 112, 749\u2013759. https:\/\/doi.org\/10.1083\/jcb.112.4.749 (1991).","journal-title":"J. Cell. Biol."},{"key":"28911_CR42","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1096\/fj.201801227R","volume":"33","author":"D Wu","year":"2019","unstructured":"Wu, D. et al. Galectin-1 promotes choroidal neovascularization and subretinal fibrosis mediated via epithelial-mesenchymal transition. Faseb j. 33, 2498\u20132513. https:\/\/doi.org\/10.1096\/fj.201801227R (2019).","journal-title":"Faseb j."},{"key":"28911_CR43","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1167\/iovs.62.2.22","volume":"62","author":"T Yamamoto","year":"2021","unstructured":"Yamamoto, T., Kanda, A., Kase, S. & Ishida, S. Hypoxia induces Galectin-1 expression via autoinduction of placental growth factor in retinal pigment epithelium cells. Invest. Ophthalmol. Vis. Sci. 62, 22. https:\/\/doi.org\/10.1167\/iovs.62.2.22 (2021).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"28911_CR44","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1186\/s12979-023-00389-x","volume":"20","author":"W Deng","year":"2023","unstructured":"Deng, W. et al. Vascular cell adhesion Molecule-1 (VCAM-1) contributes to macular fibrosis in neovascular age-related macular degeneration through modulating macrophage functions. Immun. Ageing. 20, 65. https:\/\/doi.org\/10.1186\/s12979-023-00389-x (2023).","journal-title":"Immun. Ageing"},{"key":"28911_CR45","doi-asserted-by":"publisher","first-page":"2467","DOI":"10.1016\/j.cellsig.2015.09.003","volume":"27","author":"M Agassandian","year":"2015","unstructured":"Agassandian, M. et al. VCAM-1 is a TGF-\u03b21 inducible gene upregulated in idiopathic pulmonary fibrosis. Cell. Signal. 27, 2467\u20132473. https:\/\/doi.org\/10.1016\/j.cellsig.2015.09.003 (2015).","journal-title":"Cell. Signal."},{"key":"28911_CR46","doi-asserted-by":"publisher","first-page":"e0229342","DOI":"10.1371\/journal.pone.0229342","volume":"15","author":"Y Arai","year":"2020","unstructured":"Arai, Y. et al. Aqueous humour proteins and treatment outcomes of anti-VEGF therapy in neovascular age-related macular degeneration. PLoS One. 15, e0229342. https:\/\/doi.org\/10.1371\/journal.pone.0229342 (2020).","journal-title":"PLoS One"},{"key":"28911_CR47","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1007\/978-3-642-59953-8_9","volume":"237","author":"S Davis","year":"1999","unstructured":"Davis, S. & Yancopoulos, G. D. The angiopoietins: Yin and Yang in angiogenesis. Curr. Top. Microbiol. Immunol. 237, 173\u2013185. https:\/\/doi.org\/10.1007\/978-3-642-59953-8_9 (1999).","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"28911_CR48","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.neuroscience.2019.05.038","volume":"411","author":"J Yin","year":"2019","unstructured":"Yin, J., Gong, G., Liu, X. & Angiopoietin A novel Neuroprotective\/Neurotrophic agent. Neuroscience 411, 177\u2013184. https:\/\/doi.org\/10.1016\/j.neuroscience.2019.05.038 (2019).","journal-title":"Neuroscience"},{"key":"28911_CR49","doi-asserted-by":"publisher","first-page":"1042","DOI":"10.2174\/0929866529666220825150025","volume":"29","author":"NK Oliveira","year":"2022","unstructured":"Oliveira, N. K. et al. Modified levels of Renin angiotensin related components in the frontal cortex and hippocampus were associated with neuroinflammation and lower neuroprotective effects of NGF during acute hepatic encephalopathy in mice. Protein Pept. Lett. 29, 1042\u20131050. https:\/\/doi.org\/10.2174\/0929866529666220825150025 (2022).","journal-title":"Protein Pept. Lett."},{"key":"28911_CR50","doi-asserted-by":"publisher","first-page":"4649","DOI":"10.1038\/s41598-018-22867-9","volume":"8","author":"KW Tian","year":"2018","unstructured":"Tian, K. W., Zhang, Y. Y., Jiang, H. & Han, S. Intravenous C16 and angiopoietin-1 improve the efficacy of placenta-derived mesenchymal stem cell therapy for EAE. Sci. Rep. 8, 4649. https:\/\/doi.org\/10.1038\/s41598-018-22867-9 (2018).","journal-title":"Sci. Rep."},{"key":"28911_CR51","doi-asserted-by":"publisher","first-page":"1999","DOI":"10.1167\/iovs.11-8232","volume":"53","author":"S Fujimura","year":"2012","unstructured":"Fujimura, S. et al. Angiostatic effect of CXCR3 expressed on choroidal neovascularization. Invest. Ophthalmol. Vis. Sci. 53, 1999\u20132006. https:\/\/doi.org\/10.1167\/iovs.11-8232 (2012).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"28911_CR52","first-page":"352","volume":"22","author":"F Liu","year":"2016","unstructured":"Liu, F. et al. Aqueous humor cytokine profiling in patients with wet AMD. Mol. Vis. 22, 352\u2013361 (2016).","journal-title":"Mol. Vis."},{"key":"28911_CR53","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1038\/s41598-018-19594-6","volume":"8","author":"T Sato","year":"2018","unstructured":"Sato, T., Takeuchi, M., Karasawa, Y., Enoki, T. & Ito, M. Intraocular inflammatory cytokines in patients with neovascular age-related macular degeneration before and after initiation of intravitreal injection of anti-VEGF inhibitor. Sci. Rep. 8, 1098. https:\/\/doi.org\/10.1038\/s41598-018-19594-6 (2018).","journal-title":"Sci. Rep."},{"key":"28911_CR54","doi-asserted-by":"publisher","first-page":"2301","DOI":"10.1161\/circulationaha.105.605121","volume":"113","author":"EA Heller","year":"2006","unstructured":"Heller, E. A. et al. Chemokine CXCL10 promotes atherogenesis by modulating the local balance of effector and regulatory T cells. Circulation 113, 2301\u20132312. https:\/\/doi.org\/10.1161\/circulationaha.105.605121 (2006).","journal-title":"Circulation"},{"key":"28911_CR55","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1165\/rcmb.2004-0175OC","volume":"31","author":"AM Tager","year":"2004","unstructured":"Tager, A. M. et al. Inhibition of pulmonary fibrosis by the chemokine IP-10\/CXCL10. Am. J. Respir Cell. Mol. Biol. 31, 395\u2013404. https:\/\/doi.org\/10.1165\/rcmb.2004-0175OC (2004).","journal-title":"Am. J. Respir Cell. Mol. Biol."},{"key":"28911_CR56","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1084\/jem.182.1.155","volume":"182","author":"AL Angiolillo","year":"1995","unstructured":"Angiolillo, A. L. et al. Human interferon-inducible protein 10 is a potent inhibitor of angiogenesis in vivo. J. Exp. Med. 182, 155\u2013162. https:\/\/doi.org\/10.1084\/jem.182.1.155 (1995).","journal-title":"J. Exp. Med."},{"key":"28911_CR57","doi-asserted-by":"publisher","first-page":"973025","DOI":"10.3389\/fmed.2022.973025","volume":"9","author":"J Mao","year":"2022","unstructured":"Mao, J. et al. Association between inflammatory cytokines in the aqueous humor and hyperreflective foci on optical coherence tomography in patients with neovascular age-related macular degeneration and polypoidal choroidal vasculopathy. Front. Med. (Lausanne). 9, 973025. https:\/\/doi.org\/10.3389\/fmed.2022.973025 (2022).","journal-title":"Front. Med. (Lausanne)"},{"key":"28911_CR58","first-page":"173","volume":"1","author":"AS Ho","year":"1994","unstructured":"Ho, A. S. & Moore, K. W. Interleukin-10 and its receptor. Ther. Immunol. 1, 173\u2013185 (1994).","journal-title":"Ther. Immunol."},{"key":"28911_CR59","doi-asserted-by":"publisher","first-page":"16431","DOI":"10.1523\/jneurosci.2119-15.2015","volume":"35","author":"B Siqueira Mietto","year":"2015","unstructured":"Siqueira Mietto, B. et al. Role of IL-10 in resolution of inflammation and functional recovery after peripheral nerve injury. J. Neurosci. 35, 16431\u201316442. https:\/\/doi.org\/10.1523\/jneurosci.2119-15.2015 (2015).","journal-title":"J. Neurosci."},{"key":"28911_CR60","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1046\/j.1365-2249.1999.00805.x","volume":"115","author":"IJ Crane","year":"1999","unstructured":"Crane, I. J., Kuppner, M. C., McKillop-Smith, S., Wallace, C. A. & Forrester, J. V. Cytokine regulation of granulocyte-macrophage colony-stimulating factor (GM-CSF) production by human retinal pigment epithelial cells. Clin. Exp. Immunol. 115, 288\u2013293. https:\/\/doi.org\/10.1046\/j.1365-2249.1999.00805.x (1999).","journal-title":"Clin. Exp. Immunol."},{"key":"28911_CR61","doi-asserted-by":"publisher","first-page":"2920","DOI":"10.1172\/jci31692","volume":"117","author":"C Combadi\u00e8re","year":"2007","unstructured":"Combadi\u00e8re, C. et al. CX3CR1-dependent subretinal microglia cell accumulation is associated with Cardinal features of age-related macular degeneration. J. Clin. Invest. 117, 2920\u20132928. https:\/\/doi.org\/10.1172\/jci31692 (2007).","journal-title":"J. Clin. Invest."},{"key":"28911_CR62","doi-asserted-by":"publisher","first-page":"1775","DOI":"10.1002\/emmm.201302692","volume":"5","author":"F Sennlaub","year":"2013","unstructured":"Sennlaub, F. et al. CCR2(+) monocytes infiltrate atrophic lesions in age-related macular disease and mediate photoreceptor degeneration in experimental subretinal inflammation in Cx3cr1 deficient mice. EMBO Mol. Med. 5, 1775\u20131793. https:\/\/doi.org\/10.1002\/emmm.201302692 (2013).","journal-title":"EMBO Mol. Med."},{"key":"28911_CR63","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1159\/000453550","volume":"237","author":"L Li","year":"2017","unstructured":"Li, L., Heiduschka, P., Alex, A. F., Niek\u00e4mper, D. & Eter, N. Behaviour of CD11b-Positive cells in an animal model of Laser-Induced choroidal neovascularisation. Ophthalmologica 237, 29\u201341. https:\/\/doi.org\/10.1159\/000453550 (2017).","journal-title":"Ophthalmologica"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-28911-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-28911-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-28911-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T15:54:46Z","timestamp":1781625286000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-28911-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,29]]},"references-count":63,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["28911"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-28911-9","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,29]]},"assertion":[{"value":"30 January 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 November 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Yuto Hashimoto, Hana Yoshida, Hironori Takahashi, Takuya Takayama, Shoma Tsuchiya, and Daizo Matsumoto declare that they have no competing interest. Satoru Inoda declares lecturer\u2019s fees from Kowa, Novartis, Senju, Chugai, and DeepEyeVision, Inc., and grants from Novartis, Santen, HOYA, and Chugai outside this work. Hidenori Takahashi was a founder of DeepEyeVision, Inc., and declares patents outside this work, financial support from Kyowakirin, Novartis, Linical, and Bayer outside this work, consultant fee from Nippon Boehringer Ingelheim, lecturer\u2019s fees from Santen, Kowa, Senju, Novartis, HOYA, Chugai, Viatoris, MSD, Nippon Boehringer Ingelheim, Nikon, and Bayer outside this work, and grants from Senju, Novartis and Bayer outside this work. Hidetoshi Kawashima declares lecturer\u2019s fees from Otsuka, Senju, Mitsubishi-Tanabe, Kowa, Santen, Novartis and Zeiss outside this work and grants from Senju, Linical, DeepEyeVision, HOYA, Santen, Heiwa-Iyou, and Bayer outside this work. Toshikatsu Kaburaki declares lecturer\u2019s fees from Santen, Novartis, Eizai, AbbVie, Mitsubishi-Tanabe, Kowa, Wakamoto, Senju, Ono, Ohtsuka, Daiichisankyo, Chugai, HOYA, and Alcon outside this work. Yasuo Yanagi declares grants from Santen and Novartis outside this work.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"44717"}}