Correlation of Aqueous, Vitreous, and Plasma Cytokine Levels in Patients With Proliferative Diabetic Retinopathy
Correlation of Aqueous, Vitreous, and Plasma Cytokine Levels in Patients With Proliferative Diabetic Retinopathy
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DOI：
10.1167/iovs.61.2.26
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发表时间：
2020-02-01
影响因子：
4.4
通讯作者：
Stewart, Jay M.
中科院分区：
文献类型：
--
作者：
Wu, Frances;Phone, Audrey;Stewart, Jay M.
目的.探讨增殖性糖尿病视网膜病变（PDR）患者玻璃体、房水和血浆标本中促血管生成细胞因子和炎性细胞因子之间的关系。使用多重免疫测定法分析玻璃体、房水和血浆样本中的10种PDR相关细胞因子（IL-6、IL-8、TNF-α、单核细胞趋化蛋白-1 [MCP-1]、巨噬细胞炎性蛋白-1 β [MIP-1 β]、VEGF受体1 [Flt-1]、胎盘生长因子[PlGF]、VEGF-A、VEGF-C、VEGF-D）。共纳入17例PDR患者和7例对照。主要结果是玻璃体、房水和血浆中细胞因子的相关性。次要结果是对照组和近期注射和未注射抗VEGF的糖尿病患者细胞因子水平的比较。与对照组相比，糖尿病患者中以下因子升高：玻璃体IL-6、IL-8、TNF-α、MCP-1、MIP-1 β、PlGF和VEGF-A;以及水性IL-6、IL-8、PlGF和VEGF-C（均P < 0.05）。PDR患者血清中VitA、IL-8、P1 GF、VEGF-A水平与PDR组比较差异有统计学意义（均P < 0.05）。血浆中细胞因子与玻璃体及房水中细胞因子无相关性（均P > 0.05）。在对照组和近期注射和未注射抗VEGF的糖尿病患者中，玻璃体和水性IL-6、IL-8、TNF-α、PlGF和VEGF-A存在差异（均P < 0.05）。在一对一比较中，近期注射抗VEGF药物的糖尿病患者的房水VEGF-A水平低于未注射的患者（P = 0.01）。在该概念验证研究中，IL-8、VEGF-A和PlGF在PDR患者的玻璃体和房水中表现出强相关性。对于参与PDR的某些细胞因子，房水可作为玻璃体的替代物。最近的抗VEGF注射降低了房水中的VEGF-A水平，但没有显著影响其他细胞因子，这表明其他靶向治疗在PDR管理中的作用。
PURPOSE. To investigate the relationship between proangiogenic and inflammatory cytokines in concurrent vitreous, aqueous, and plasma samples from patients with proliferative diabetic retinopathy (PDR).METHODS. Vitreous, aqueous, and plasma samples were analyzed using multiplex immunoassay for 10 PDR-related cytokines (IL-6, IL-8, TNF-alpha, monocyte chemoattractant protein-1 [MCP-1], macrophage inflammatory protein-1 beta [MIP-1 beta], VEGF receptor 1 [Flt-1], placental growth factor [PlGF], VEGF-A, VEGF-C, VEGF-D). A total of 17 patients with PDR and 7 controls were included. The primary outcome was correlation of cytokines in vitreous, aqueous, and plasma. The secondary outcome was the comparison of cytokine levels in controls and diabetics with and without recent anti-VEGF injection.RESULTS. The following factors were elevated in diabetics compared with controls: vitreous IL-6, IL-8, TNF-alpha, MCP-1, MIP-1 beta, PlGF, and VEGF-A; and aqueous IL-6, IL-8, PlGF, and VEGF-C (all P < 0.05). Vitreous and aqueous IL-8, PlGF, and VEGF-A were significantly correlated in patients with PDR (all P < 0.05). Plasma cytokines were not correlated with those in vitreous and aqueous (all P > 0.05). Vitreous and aqueous IL-6, IL-8, TNF-alpha, PlGF, and VEGF-A differed among controls and diabetics with and without recent anti-VEGF injection (all P < 0.05). In one-to-one comparisons, aqueous VEGF-A levels were lower in diabetic patients who had recent anti-VEGF injection compared with those who did not (P = 0.01).CONCLUSIONS. In this proof-of-concept study, IL-8, VEGF-A, and PlGF demonstrated a strong correlation in vitreous and aqueous of patients with PDR. The aqueous may serve as a proxy for vitreous for some cytokines involved in PDR. Recent anti-VEGF injections decreased VEGF-A levels in aqueous, but did not significantly affect other cytokines, suggesting a role for other targeted therapies in PDR management.