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评估晚期糖基化终产物和血管生成因子的玻璃体水平作为糖尿病视网膜病变严重程度的生物标志物。

Evaluation of vitreous levels of advanced glycation end products and angiogenic factors as biomarkers for severity of diabetic retinopathy.

作者信息

Katagiri Makiko, Shoji Jun, Inada Noriko, Kato Satoshi, Kitano Shigehiko, Uchigata Yasuko

机构信息

Department of Ophthalmology, Diabetes Center, Tokyo Women's Medical University School of Medicine, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.

Division of Ophthalmology, Department of Visual Sciences, Nihon University School of Medicine, Tokyo, Japan.

出版信息

Int Ophthalmol. 2018 Apr;38(2):607-615. doi: 10.1007/s10792-017-0499-1. Epub 2017 Mar 15.

Abstract

BACKGROUND/AIMS: Glyceraldehyde-derived advanced glycation end products (glycer-AGE; also called Toxic-AGE [TAGE]) play a crucial role in the pathogenesis of diabetic angiopathy. However, the relationships between vitreous glycer-AGE levels and diabetic retinopathy (DR) severity, and between glycer-AGE levels and the levels of other angiogenic factors remain unknown. We investigated the correlation between levels of vitreous biomarkers, including glycer-AGE and angiogenic factors (vascular endothelial growth factor [VEGF], interleukin [IL]-8, leptin, placental growth factor [PlGF], endoglin, and fibroblast growth factor [FGF]-2) in patients with DR, using three DR staging groups.

METHODS

In this cross-sectional study, we examined 33 eyes from 33 patients with diabetes mellitus who underwent a vitrectomy (non-proliferative DR [NPDR, n = 8]; PDR with simple vitreous haemorrhage [VH, n = 17]; or PDR with a fibrovascular proliferative membrane [FVM, n = 8]). Vitreous levels of glycer-AGE and VEGF were evaluated using enzyme-linked immunosorbent assays. Vitreous levels of IL-8, leptin, PlGF, endoglin, and FGF-2 were evaluated using beaded assay methods.

RESULTS

Vitreous levels of glycer-AGE in the FVM group were significantly higher than those in the NPDR and VH groups (all p < 0.05). Vitreous levels of VEGF (r = 0.85, p = 1.7 × 10) and leptin (r = 0.60, p = 5.0 × 10) were significantly correlated with levels of PlGF.

CONCLUSION

The two systems (VEGF-PlGF-leptin and glycer-AGE) were represented in these measured biomarkers. High vitreous levels of both VEGF and glycer-AGE may be linked to more severe DR, suggesting that anti-VEGF and anti-TAGE therapy may be an important part of the therapeutic strategy for DR.

摘要

背景/目的:甘油醛衍生的晚期糖基化终产物(甘油-AGE;也称为毒性-AGE [TAGE])在糖尿病血管病变的发病机制中起关键作用。然而,玻璃体液中甘油-AGE水平与糖尿病视网膜病变(DR)严重程度之间的关系,以及甘油-AGE水平与其他血管生成因子水平之间的关系仍不清楚。我们使用三个DR分期组,研究了DR患者玻璃体液生物标志物水平之间的相关性,这些生物标志物包括甘油-AGE和血管生成因子(血管内皮生长因子 [VEGF]、白细胞介素 [IL]-8、瘦素、胎盘生长因子 [PlGF]、内皮糖蛋白和成纤维细胞生长因子 [FGF]-2)。

方法

在这项横断面研究中,我们检查了33例接受玻璃体切除术的糖尿病患者的33只眼睛(非增殖性DR [NPDR,n = 8];伴有单纯玻璃体出血 [VH] 的PDR,n = 17;或伴有纤维血管增殖膜 [FVM] 的PDR,n = 8])。使用酶联免疫吸附测定法评估玻璃体液中甘油-AGE和VEGF的水平。使用微珠测定法评估玻璃体液中IL-8、瘦素、PlGF、内皮糖蛋白和FGF-2的水平。

结果

FVM组玻璃体液中甘油-AGE水平显著高于NPDR组和VH组(所有p < 0.05)。玻璃体液中VEGF(r = 0.85,p = 1.7 × 10)和瘦素(r = 0.60,p = 5.0 × 10)的水平与PlGF的水平显著相关。

结论

在这些测量的生物标志物中体现了两个系统(VEGF-PlGF-瘦素和甘油-AGE)。玻璃体液中VEGF和甘油-AGE的高水平可能与更严重的DR相关,这表明抗VEGF和抗TAGE治疗可能是DR治疗策略的重要组成部分。

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