Ambati J, Chalam K V, Chawla D K, D'Angio C T, Guillet E G, Rose S J, Vanderlinde R E, Ambati B K
Department of Ophthalmology, University of Rochester, NY, USA.
Arch Ophthalmol. 1997 Sep;115(9):1161-6. doi: 10.1001/archopht.1997.01100160331011.
To examine the relative levels of gamma-aminobutyric acid (GABA), glutamate, and vascular endothelial growth factor (VEGF) in the vitreous of nondiabetic and diabetic patients.
Undiluted vitreous samples were obtained from 22 patients with proliferative diabetic retinopathy (PDR) and 28 patients without diabetes who underwent pars plana vitrectomy. Simultaneous venous blood samples also were obtained. Amino acid concentrations were determined using sensitive high-performance liquid chromatography, and VEGF levels by quantitative enzyme-linked immunosorbent assay. Hemoglobin concentrations in the blood and vitreous were determined using spectrophotometry.
The level of GABA in the vitreous of patients with PDR, 29.4 +/- 7.8 mumol/L, was significantly higher than in controls (18.4 +/- 5.5 mumol/L) (P = .004). The vitreous concentration of glutamate was higher in patients with PDR (24.7 +/- 14.0 mumol/L) compared with controls (9.1 +/- 5.1 mumol/L) (P < .001). Vitreous VEGF level was significantly higher in patients with PDR (1759 +/- 1721 pg/mL) compared with controls (27 +/- 65 pg/mL) (P < .001). There were moderately strong correlations between GABA and VEGF levels (r = 0.68) and glutamate and VEGF levels (r = 0.43). Elevated GABA, glutamate, and VEGF levels also correlated strongly with the presence of PDR. Correcting for possible introduction of these molecules by vitreous hemorrhage did not significantly alter these findings.
Levels of glutamate potentially toxic to retinal ganglion cells are found in the vitreous of patients with PDR. Elevated vitreous GABA may reflect amacrine cell dysfunction and underlie electroretinographic oscillatory potential abnormalities seen in diabetic retinopathy. The correlations of glutamate and GABA levels with an elevated VEGF level provide biochemical support for ischemia-induced neovascularization in patients with PDR. These findings present opportunities for novel therapeutic modalities in the treatment of PDR.
检测非糖尿病患者和糖尿病患者玻璃体内γ-氨基丁酸（GABA）、谷氨酸和血管内皮生长因子（VEGF）的相对水平。
从22例接受玻璃体切割术的增殖性糖尿病视网膜病变（PDR）患者和28例非糖尿病患者中获取未稀释的玻璃体样本。同时采集静脉血样本。使用灵敏的高效液相色谱法测定氨基酸浓度，通过定量酶联免疫吸附测定法测定VEGF水平。使用分光光度法测定血液和玻璃体内的血红蛋白浓度。
PDR患者玻璃体内GABA水平为29.4±7.8μmol/L，显著高于对照组（18.4±5.5μmol/L）（P = 0.004）。PDR患者玻璃体内谷氨酸浓度（24.7±14.0μmol/L）高于对照组（9.1±5.1μmol/L）（P < 0.001）。PDR患者玻璃体内VEGF水平（1759±1721 pg/mL）显著高于对照组（27±65 pg/mL）（P < 0.001）。GABA与VEGF水平（r = 0.68）以及谷氨酸与VEGF水平（r = 0.43）之间存在中度强相关性。GABA、谷氨酸和VEGF水平升高也与PDR的存在密切相关。校正玻璃体积血可能引入这些分子的影响后，这些结果无显著改变。
在PDR患者的玻璃体内发现了对视网膜神经节细胞具有潜在毒性的谷氨酸水平。玻璃体内GABA升高可能反映无长突细胞功能障碍，并是糖尿病视网膜病变中视网膜电图振荡电位异常的基础。谷氨酸和GABA水平与升高的VEGF水平之间的相关性为PDR患者缺血诱导的新生血管形成提供了生化支持。这些发现为PDR的治疗提供了新的治疗方式的机会。
