{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T16:38:05Z","timestamp":1768322285714,"version":"3.49.0"},"reference-count":70,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T00:00:00Z","timestamp":1751587200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Surgery Department research budget at the Faculty of Medicine and Odontology of the University of Valencia (Valencia, Spain)","award":["REI-RICORS RD21\/0002\/0032"],"award-info":[{"award-number":["REI-RICORS RD21\/0002\/0032"]}]},{"name":"Surgery Department research budget at the Faculty of Medicine and Odontology of the University of Valencia (Valencia, Spain)","award":["RD24\/0007\/0004"],"award-info":[{"award-number":["RD24\/0007\/0004"]}]},{"name":"Spanish Network of Inflammation and Immunopathology of Organs and Systems","award":["REI-RICORS RD21\/0002\/0032"],"award-info":[{"award-number":["REI-RICORS RD21\/0002\/0032"]}]},{"name":"Spanish Network of Inflammation and Immunopathology of Organs and Systems","award":["RD24\/0007\/0004"],"award-info":[{"award-number":["RD24\/0007\/0004"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Type 2 diabetes mellitus (T2DM) is a major public health concern that significantly increases the risk of diabetic retinopathy (DR), a leading cause of visual impairment worldwide. This study aimed to identify molecular markers of inflammation (INF) and angiogenesis (ANG) in the aqueous humor (AH) of patients with non-proliferative diabetic retinopathy (NPDR). We conducted an observational, multicenter, case\u2013control study including 116 participants classified into T2DM with NPDR, T2DM without DR, and non-diabetic controls (SCG) undergoing cataract surgery. AH samples were collected intraoperatively and analyzed for 27 cytokines using multiplex immunoassay. Eighteen immune mediators were detected in AH samples, and several were significantly elevated in the NPDR group, including the interleukins (IL) -1\u03b2, -6, -8, -15, -17, as well as the granulocyte\u2013macrophage colony stimulating factor (GM-CSF), basic fibroblast growth factor (bFGF), interferon gamma-induced protein (IP-10), macrophage inflammatory protein 1 beta (MIP-1b), monocyte chemoattractant protein-1 (MCP-1), regulated on activation, normal T cell-expressed and -secreted protein (RANTES), and the vascular endothelial growth factor (VEGF). These molecules are involved in retinal INF, blood\u2013retinal barrier breakdown, and pathological neovascularization. Our findings reveal a distinct pro-INF and pro-ANG profile in the AH of NPDR patients, suggesting that these cytokines may serve as early diagnostic\/prognostic biomarkers for DR. Targeting these molecules could provide novel therapeutic strategies to mitigate retinal damage and vision loss in diabetic patients.<\/jats:p>","DOI":"10.3390\/ijms26136461","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T08:58:23Z","timestamp":1751878703000},"page":"6461","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exploring Molecular Signatures Associated with Inflammation and Angiogenesis in the Aqueous Humor of Patients with Non-Proliferative Diabetic Retinopathy"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8550-4392","authenticated-orcid":false,"given":"V\u00edctor","family":"Alegre-Ituarte","sequence":"first","affiliation":[{"name":"Cellular and Molecular Ophthalmo-Biology Group (GIUV 13\/152), Department of Surgery, Faculty of Medicine and Odontology, University of Valencia, 46010 Valencia, Spain"},{"name":"Ophthalmic Research Unit \u201cSantiago Grisol\u00eda\u201d\/FISABIO, 46017 Valencia, Spain"},{"name":"Ophthalmology Service, Complex Hospitalari Universitari Mois\u00e8s Broggi, 08970 Sant Joan Desp\u00ed, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2112-8217","authenticated-orcid":false,"given":"Irene","family":"Andr\u00e9s-Blasco","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Ophthalmo-Biology Group (GIUV 13\/152), Department of Surgery, Faculty of Medicine and Odontology, University of Valencia, 46010 Valencia, Spain"},{"name":"Ophthalmic Research Unit \u201cSantiago Grisol\u00eda\u201d\/FISABIO, 46017 Valencia, Spain"},{"name":"Spanish Network of Inflammatory Diseases and Immunopathology of Organs and Systems (REI-RICORS; RD24\/0007\/0004), Institute of Health Carlos III, Ministry of Science and Innovation, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Pe\u00f1a-Ruiz","sequence":"additional","affiliation":[{"name":"Ophthalmology Service, University Clinic Hospital, 47003 Valladolid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvatore","family":"Di Lauro","sequence":"additional","affiliation":[{"name":"Ophthalmology Service, University Clinic Hospital, 47003 Valladolid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Crespo-Millas","sequence":"additional","affiliation":[{"name":"Ophthalmology Service, University Clinic Hospital, 47003 Valladolid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3725-8211","authenticated-orcid":false,"given":"Alessio","family":"Martucci","sequence":"additional","affiliation":[{"name":"Ophthalmology Service, University of Roma Tor Vergata, 00133 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge","family":"Vila-Arteaga","sequence":"additional","affiliation":[{"name":"Ophthalmology Service, University and Polytechnic Hospital La Fe, 46026 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0118-7837","authenticated-orcid":false,"given":"Mar\u00eda Dolores","family":"Pinazo-Dur\u00e1n","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Ophthalmo-Biology Group (GIUV 13\/152), Department of Surgery, Faculty of Medicine and Odontology, University of Valencia, 46010 Valencia, Spain"},{"name":"Ophthalmic Research Unit \u201cSantiago Grisol\u00eda\u201d\/FISABIO, 46017 Valencia, Spain"},{"name":"Spanish Network of Inflammatory Diseases and Immunopathology of Organs and Systems (REI-RICORS; RD24\/0007\/0004), Institute of Health Carlos III, Ministry of Science and Innovation, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Galarreta","sequence":"additional","affiliation":[{"name":"Ophthalmology Service, University Clinic Hospital, 47003 Valladolid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juli\u00e1n","family":"Garc\u00eda-Feijoo","sequence":"additional","affiliation":[{"name":"Ophthalmology Service, University Clinic Hospital San Carlos, 28040 Madrid, Spain"},{"name":"Institute of Health Research, San Carlos Clinic Hospital (IdISSC), 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1016\/j.ophtha.2021.04.027","article-title":"Global Prevalence of Diabetic Retinopathy and Projection of Burden through 2045: Systematic Review and Meta-analysis","volume":"128","author":"Teo","year":"2021","journal-title":"Ophthalmology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"556","DOI":"10.2337\/dc11-1909","article-title":"Global prevalence and major risk factors of diabetic retinopathy","volume":"35","author":"Yau","year":"2012","journal-title":"Diabetes Care"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.ophtha.2008.10.016","article-title":"The Wisconsin Epidemiologic Study of Diabetic Retinopathy XXIII: The twenty-five-year incidence of macular edema in persons with type 1 diabetes","volume":"116","author":"Klein","year":"2009","journal-title":"Ophthalmology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/s41574-020-00451-4","article-title":"Current understanding of the molecular and cellular pathology of diabetic retinopathy","volume":"17","author":"Antonetti","year":"2021","journal-title":"Nat. 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