Vitreous Levels of Reactive Oxygen Species in Proliferative Diabetic Retinopathy
Date Issued
2007
Date
2007
Author(s)
DOI
zh-TW
Abstract
Microangiopathies are the major cause of morbidity and mortality of diabetes mellitus (DM), contributing to diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy. Oxidative stress might have an important role in the modulation of vascular smooth muscle cell growth and migration, endothelial function, and extracellular matrix formation. Many biochemical pathways are altered under hyperglycemic conditions, leading to increased generation of reactive oxygen species (ROS) and enhanced oxidative stress within tissues. In addition, total antioxidant defense capacities are reduced in plasma when oxidative stress is significantly increased.
Oxidative stress might be particularly important in the development of diabetic retinopathy because the retina has a high demand for oxygen and a high unsaturated lipid content. These unique features lead to the increased production of ROS and hyperoxidative lipids through lipid peroxidation and altered biochemical reactions. Furthermore, the severity of diabetic retinopathy is more affected by locally produced oxidative substances than by those that diffuse from the serum.
In the pathogenesis of diabetic retinopathy, vascular endothelial growth factor (VEGF) and angiopoietin 2 are potent angiogenic peptides that mediate ischemia-induced retinal neovascularization. VEGF and angiopoietin 2 levels are elevated in the vitreous fluid of patients with proliferative diabetic retinopathy (PDR) and might induce vascular endothelial cell proliferation in vivo. Several reports suggest that ROS are strongly correlated with increased VEGF and angiopoietin 2 expression.
We hypothesized that eyes with diabetic retinopathy have a higher level of intraocular ROS than nondiabetic eyes, and that the ROS level within the vitreous reflects different degrees of severity of diabetic retinopathy. In the present study, we investigate vitreous levels of reactive oxygen species (ROS) in patients with proliferative diabetic retinopathy (PDR) and analyze ROS levels among different groups of patients with PDR.
There were thirty-nine eyes of 39 patients with PDR and 16 eyes of 16 non-PDR patients (control group) who underwent primary pars plana vitrectomy for complications of PDR and other ocular diseases (control group) were enrolled, with patients’ follow-up time more than 12 months.
PDR patients were classified into 3 groups according to extent of fibrovascular proliferation. Group 1 (n=17): none or focal adhesion ≤ 3 sites; Group 2 (n=12): broad adhesion ≥ 1 site(s) or vitreous-retinal adhesion around disc, macula, or arcade; Group 3 (n=10): vitreous-retinal attachment extending to periphery or no posterior vitreous detachment with or without retinal detachment; Control group (n = 16): non-PDR patients. Demographic data, clinical findings and course recorded. Vitreous samples obtained during vitrectomy and vitreous levels of ROS measured by Luminol-enhanced chemiluminescence (CL) assay.
ROS levels recorded as mean ± standard deviation (SD) CL counts/10s. Correlations of vitreous levels of ROS among different groups of PDR and anatomic prognosis evaluated. Multiple linear regression analysis of selective potential risk factors performed to investigate the main determinants of ROS levels.
Vitreous level of ROS was significantly higher in patients with PDR (125.76 ± 351.72 CL counts/10s) than in control patients (0.37 ± 0.72 CL counts/10s) (P<0.0001). ROS levels (CL counts/10s) in Groups 1, 2, and 3 were 1.86 ± 1.63, 24.47 ± 22.68, and 457.94 ± 597.01, respectively; the difference among groups was significant (P=0.001). Regression analysis showed only patient grouping (according to severity of fibrovascular proliferation) manifested strongest dependent association with ROS levels (P=0.001). Final anatomic results revealed that recurrent untreatable retinal detachment occurred in 3 patients of Group 3, who also had the highest ROS levels (1784.40; 1076.22 and 896.29 CL counts/10s).
In conclusion, our results suggest that ROS levels are significantly elevated in the vitreous fluid of PDR patients, and that ROS levels correlate with the severity of PDR. Quantification of the vitreous levels of ROS might be an indicator of the anatomic results and more aggressive treatments, such as combined scleral buckling, silicone oil infusion, or intravitreal anti-VEGF agent injection should be undertaken during surgery. These findings suggest an important association of ROS and the pathogenesis of diabetic retinopathy. Further extended studies are needed to elucidate whether the reduction of ROS by free radical scavenger therapies might be a new approach for inhibiting the development of diabetic retinopathy.
Subjects
化學發光
糖尿病視網膜病變
活性氧
玻璃體
chemiluminescence
diabetic retinopathy
reactive oxygen species
vitreous
SDGs
Type
text
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