Alegre-Ituarte Víctor, Andrés-Blasco Irene, Peña-Ruiz David, Di Lauro Salvatore, Crespo-Millas Sara, Martucci Alessio, Vila-Arteaga Jorge, Pinazo-Durán María Dolores, Galarreta David, García-Feijoo Julián
Cellular and Molecular Ophthalmo-Biology Group (GIUV 13/152), Department of Surgery, Faculty of Medicine and Odontology, University of Valencia, 46010 Valencia, Spain.
Ophthalmic Research Unit "Santiago Grisolía"/FISABIO, 46017 Valencia, Spain.
Int J Mol Sci. 2025 Jul 4;26(13):6461. doi: 10.3390/ijms26136461.
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-control 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) -1β, -6, -8, -15, -17, as well as the granulocyte-macrophage 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-retinal 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.
2型糖尿病（T2DM）是一个重大的公共卫生问题，它显著增加了糖尿病视网膜病变（DR）的风险，而DR是全球视力损害的主要原因。本研究旨在确定非增殖性糖尿病视网膜病变（NPDR）患者房水（AH）中炎症（INF）和血管生成（ANG）的分子标志物。我们进行了一项观察性、多中心、病例对照研究，纳入了116名参与者，他们被分为患有NPDR的T2DM患者、无DR的T2DM患者以及接受白内障手术的非糖尿病对照组（SCG）。术中采集AH样本，并使用多重免疫测定法分析27种细胞因子。在AH样本中检测到18种免疫介质，其中几种在NPDR组中显著升高，包括白细胞介素（IL）-1β、-6、-8、-15、-17，以及粒细胞巨噬细胞集落刺激因子（GM-CSF）、碱性成纤维细胞生长因子（bFGF）、干扰素γ诱导蛋白（IP-10）、巨噬细胞炎性蛋白1β（MIP-1b）、单核细胞趋化蛋白-1（MCP-1）、活化调节正常T细胞表达和分泌蛋白（RANTES）以及血管内皮生长因子（VEGF）。这些分子参与视网膜INF、血视网膜屏障破坏和病理性新生血管形成。我们的研究结果揭示了NPDR患者AH中独特的促INF和促ANG特征，表明这些细胞因子可能作为DR的早期诊断/预后生物标志物。针对这些分子可能提供新的治疗策略，以减轻糖尿病患者的视网膜损伤和视力丧失。
