Nishiguchi Koji M, Ushida Hiroaki, Tomida Daisuke, Kachi Shu, Kondo Mineo, Terasaki Hiroko
Department of Ophthalmology, Nagoya University School of Medicine, Showa-ku, Nagoya, Japan.
Mol Vis. 2013 May 29;19:1125-31. Print 2013.
To assess the relationship between intraocular soluble heparan sulfate (HS) concentration and age in subjects with and without diabetic retinopathy.
Vitreous from subjects with idiopathic maculopathies (n=17), i.e., macula hole or epiretinal membrane, or nonproliferative diabetic retinopathy (non-PDR; n=5) and aqueous humor from subjects with PDR (n=16), non-PDR (n=7), or cataracts (n=15) was collected. The levels of HS and vascular endothelial growth factor (VEGF) were measured using enzyme-linked immunosorbent assay. Concentrations of sulfated glycosaminoglycan were determined through dimethylmethylene blue-based assay. The effect of the vitreal HS level on the binding of exogenous VEGF to surface-bound heparin was determined in vitro.
The level of HS in vitreous samples from subjects with idiopathic maculopathies increased concomitantly with age (p=0.020, R²=0.327). Meanwhile, HS levels in aqueous humor were lower in PDR subjects than in non-PDR (p=0.003) and cataract subjects (p=0.007). However, the PDR subjects were significantly younger than the non-PDR subjects (p<0.001) or cataract subjects (p<0.001). When the three groups were controlled for age, the levels of HS glycosaminoglycans were no longer different between the three (p=0.247). The increasing level of HS or sulfated glycosaminoglycan in the vitreous was associated with its increased inhibitory effect on interaction between VEGF and surface heparin in vitro (p=0.014, R²=0.377).
The HS level of the intraocular fluid increased with age. The possible link between low HS in intraocular fluid and increased localization of VEGF at the retinal surface may provide one explanation for the higher susceptibility of younger subjects with diabetes mellitus to developing PDR.
评估患有和未患有糖尿病视网膜病变的受试者眼内可溶性硫酸乙酰肝素（HS）浓度与年龄之间的关系。
收集患有特发性黄斑病变（n = 17），即黄斑裂孔或视网膜前膜的受试者的玻璃体，或非增殖性糖尿病视网膜病变（非PDR；n = 5）的受试者的玻璃体，以及患有增殖性糖尿病视网膜病变（PDR；n = 16）、非PDR（n = 7）或白内障（n = 15）的受试者的房水。使用酶联免疫吸附测定法测量HS和血管内皮生长因子（VEGF）的水平。通过基于二甲基亚甲基蓝的测定法确定硫酸化糖胺聚糖的浓度。在体外确定玻璃体HS水平对外源性VEGF与表面结合肝素结合的影响。
患有特发性黄斑病变的受试者玻璃体样本中的HS水平随年龄增长而升高（p = 0.020，R² = 0.327）。同时，PDR受试者房水中的HS水平低于非PDR受试者（p = 0.003）和白内障受试者（p = 0.007）。然而，PDR受试者明显比非PDR受试者（p < 0.001）或白内障受试者（p < 0.001）年轻。当对三组进行年龄校正后，三组之间HS糖胺聚糖的水平不再有差异（p = 0.247）。玻璃体中HS或硫酸化糖胺聚糖水平的升高与其在体外对VEGF与表面肝素之间相互作用的抑制作用增强相关（p = 0.014，R² = 0.377）。
眼内液中的HS水平随年龄增长而升高。眼内液中低HS与VEGF在视网膜表面定位增加之间的可能联系，可能为年轻糖尿病患者更易发生PDR提供一种解释。
