Katagiri Makiko, Shoji Jun, Inada Noriko, Kato Satoshi, Kitano Shigehiko, Uchigata Yasuko
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.
Int Ophthalmol. 2018 Apr;38(2):607-615. doi: 10.1007/s10792-017-0499-1. Epub 2017 Mar 15.
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.
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.
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.
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.
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）。
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。
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。
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。
