Honkanen Robert A, Baruah Sankar, Zimmerman M Bridget, Khanna Cheryl L, Weaver Yaffa K, Narkiewicz Joanna, Waziri Rafiq, Gehrs Karen M, Weingeist Thomas A, Boldt H Culver, Folk James C, Russell Stephen R, Kwon Young H
Department of Ophthalmology and Visual Sciences, University of Iowa Hospitals and Clinics, 200 Hawkins Dr, Iowa City, IA 52242, USA.
Arch Ophthalmol. 2003 Feb;121(2):183-8. doi: 10.1001/archopht.121.2.183.
To measure vitreous concentrations of glutamate and other amino acids in patients with glaucoma undergoing vitrectomy.
Undiluted vitreous samples were collected from patients undergoing vitrectomy at the University of Iowa (Iowa City) between 1997 and 1998 (n = 69). Vitreous concentrations of 16 amino acids, including glutamate, were determined using high-pressure liquid chromatography. Patients with a history of diabetes mellitus were excluded from the analysis. The study group consisted of those with a history of glaucoma (n = 8), and the control group included those with an epiretinal membrane and/or macular hole with no history of glaucoma (n = 17). Comparison of amino acid concentrations between the 2 groups was performed using a multifactor main effects model that adjusted for the effect of 10 selected covariates. Power analysis was done to determine the level of significant difference in amino acid concentrations.
The glaucoma group comprised vitreal specimens from patients with primary open-angle (n = 3) and angle-closure glaucomas that included aqueous misdirection (n = 2), uveitis with secondary angle-closure (n = 2), and Axenfeld Rieger syndrome (n = 1). Indications for vitrectomy in this group included epiretinal membrane, retinal detachment, aqueous misdirection, and uveitis. The control group included specimens from patients with a macular hole (n = 11) and epiretinal membrane (n = 7), with 1 eye having both. Surgical indications in controls were macular hole, retinal detachment, and epiretinal membrane. The mean +/- SD levels of vitreous glutamate, glycine, gamma-aminobutyric acid, and alanine were 6.1 +/- 2.4, 16.3 +/- 7.5, 0.8 +/- 0.3, and 260.5 +/- 101.9 microM, respectively, in glaucoma and 5.2 +/- 2.3, 8.5 +/- 2.5, 0.6 +/- 0.2, and 159.5 +/- 54.9 microM in controls (P >.05 for all). None of the 16 amino acid concentrations measured showed a statistically significant difference between glaucoma and controls (P values between.06 and >.99). A power analysis indicated that a 1.8-fold elevation in the glutamate level was needed to reach significance.
Vitreous amino acid concentrations.
None of the 16 amino acids measured, including glutamate, were significantly elevated in the vitreous of glaucomatous eyes compared with controls. Our results are not consistent with the simple hypothesis of glutamate excitotoxicity in glaucoma. Instead, our findings indicate the dynamic nature of extracellular glutamate, whose concentration is dependent on complex mechanisms not yet fully understood. Further studies are needed to fully elucidate the role of glutamate in the pathogenesis of glaucoma.
测量接受玻璃体切除术的青光眼患者玻璃体内谷氨酸及其他氨基酸的浓度。
1997年至1998年期间,从爱荷华大学(爱荷华城)接受玻璃体切除术的患者中收集未稀释的玻璃体样本(n = 69)。使用高压液相色谱法测定包括谷氨酸在内的16种氨基酸的玻璃体浓度。有糖尿病病史的患者被排除在分析之外。研究组由有青光眼病史的患者组成(n = 8),对照组包括有视网膜前膜和/或黄斑裂孔且无青光眼病史的患者(n = 17)。使用多因素主效应模型对两组氨基酸浓度进行比较,该模型对10个选定协变量的效应进行了校正。进行功效分析以确定氨基酸浓度的显著差异水平。
青光眼组包括原发性开角型青光眼患者的玻璃体标本(n = 3)和闭角型青光眼患者的标本,其中包括房水错流(n = 2)、伴有继发性闭角型青光眼的葡萄膜炎(n = 2)和Axenfeld-Rieger综合征(n = 1)。该组玻璃体切除术的指征包括视网膜前膜、视网膜脱离、房水错流和葡萄膜炎。对照组包括黄斑裂孔患者(n = 11)和视网膜前膜患者(n = 7)的标本,其中1只眼同时患有这两种疾病。对照组的手术指征为黄斑裂孔、视网膜脱离和视网膜前膜。青光眼组玻璃体内谷氨酸、甘氨酸、γ-氨基丁酸和丙氨酸的平均±标准差水平分别为6.1±2.4、16.3±7.5、0.8±0.3和260.5±101.9μM,对照组分别为5.2±2.3、8.5±2.5、0.6±0.2和159.5±54.9μM(所有P>.05)。所测量的16种氨基酸浓度在青光眼组和对照组之间均未显示出统计学上的显著差异(P值在0.06至>.99之间)。功效分析表明,谷氨酸水平需要升高1.8倍才能达到显著水平。
玻璃体内氨基酸浓度。
与对照组相比,在青光眼患者的玻璃体中,所测量的16种氨基酸(包括谷氨酸)均未显著升高。我们的结果与青光眼谷氨酸兴奋性毒性的简单假设不一致。相反,我们的研究结果表明细胞外谷氨酸的动态性质,其浓度取决于尚未完全理解的复杂机制。需要进一步研究以充分阐明谷氨酸在青光眼发病机制中的作用。