Homocysteine Levels in the Vitreous of Proliferative Diabetic Retinopathy and Rhegmatogenous Retinal Detachment: Its Modulating Role on Lysyl Oxidase

Homocysteine Levels in the Vitreous of Proliferative Diabetic Retinopathy and Rhegmatogenous Retinal Detachment: Its Modulating Role on Lysyl Oxidase
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DOI:
10.1167/iovs.08-2667
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发表时间:
2009-08-01
影响因子:
4.4
通讯作者:
Rupak, Roy
Rupak, Roy
中科院分区:
医学2区
文献类型:
--
作者:
Coral, Karunakaran;Angayarkanni, Narayanasamy;Rupak, Roy

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目的.同型半胱氨酸(Homocysteine,Hcys)是一种常见的血管内皮细胞损伤诱导剂,与细胞外基质的变化密切相关。赖氨酰氧化酶(LOX)是一种铜依赖性胺氧化酶,其引发细胞外基质(ECM)中胶原蛋白和弹性蛋白的共价交联。LOX有助于ECM的结构完整性,并且低LOX活性可促进ECM解体。羟脯氨酸水平用于预测胶原蛋白周转状态,并且存在于生物流体中的大多数内源性羟脯氨酸来源于各种形式的胶原蛋白的降解。由于已知HCys调节ECM周转并且还抑制LOX活性,因此本研究的目的是估计患有增殖性糖尿病视网膜病变(PDR)和孔源性视网膜脱离(RRD)的眼睛中HCys的玻璃体水平,并且关联HCys(如果有的话)对LOX活性的影响。使用在PDR(n = 18)和RRD(n = 17)的玻璃体视网膜手术期间获得的未稀释的人玻璃体标本。取供者眼球玻璃体标本作为对照(n = 19)。通过HPLC使用荧光检测器估计HCys。羟脯氨酸是通过化学计量学估计的。PDR(P = 0.011)和RRD(P = 0.001)患者玻璃体总Hcys水平均显著高于对照组。与对照组相比,PDR(P = 0.049)和RRD(P = 0.007)中的羟脯氨酸水平显著升高。PDR组(P = 0.040)和RRD组(P = 0.029)的Hcy水平与LOX比活性呈显著负相关。该报告显示,PDR和RRD中玻璃体Hcys的增加与LOX特异性活性的显著降低相关,沿着胶原周转的增加。(Invest Ophthalmol维斯科学。2009;50:3607-3612)DOI:10.1167/iovs.08-2667
PURPOSE. Homocysteine (Hcys), a well-known inducer of vascular endothelial cell damage has been associated with extracellular matrix changes. Lysyl oxidase (LOX) is a copper-dependent amine oxidase that initiates the covalent cross-linking of collagen and elastin in the extracellular matrix (ECM). LOX contributes to the structural integrity of the ECM, and low LOX activity could promote ECM disorganization. Hydroxyproline levels are used to predict collagen turnover status, and most of the endogenous hydroxyproline present in biological fluids is derived from the degradation of various forms of collagen. As Hcys is known to regulate ECM turnover and also inhibit LOX activity, the purpose of this study was to estimate the vitreous levels of Hcys in eyes with proliferative diabetic retinopathy (PDR) and rhegmatogenous retinal detachment (RRD) and to correlate the effect of Hcys, if any on LOX activity.METHODS. Undiluted human vitreous specimens obtained during vitreoretinal surgeries for PDR (n = 18) and RRD (n = 17) were used. Vitreous specimens from donor eyeballs were used as control (n = 19). Hcys was estimated by HPLC using a fluorescent detector. Hydroxyproline was estimated spectrophotometrically.RESULTS. The total vitreous Hcys level was found to be increased significantly in PDR (P = 0.011) and in RRD (P = 0.001) compared with that in control samples. Hydroxyproline was significantly increased in PDR (P = 0.049) and RRD (P = 0.007) compared with the level in control samples. There was a significant negative correlation between the Hcys level and the specific activity of LOX in PDR (P = 0.040) and in RRD (P = 0.029)CONCLUSIONS. This report shows that increased vitreous Hcys in PDR and RRD is associated with a significant decrease in LOX-specific activity along with an increase in collagen turnover. (Invest Ophthalmol Vis Sci. 2009;50:3607-3612) DOI:10.1167/iovs.08-2667