糖尿病视网膜病变(diabetes retinopathy, DR)是糖尿病常见的眼部并发症,其病理过程复杂,涉及多种细胞及炎症因子。Müller细胞作为视网膜主要支持细胞,在DR中不仅产生白介素-17(interleukin-17, IL-17),还作为其主要靶点发挥作用,通过谷氨酸代谢异常、血管内皮生长因子(vascular endothelial growth factor, VEGF)分泌增加及调控参与DR的病理过程,加重炎症反应。IL-17主要由辅助性T细胞17(T helper cell 17, Th17)分泌,通过促进多种炎症介质(如细胞因子、趋化因子和金属蛋白酶)的分泌,增强炎症反应,导致视网膜微血管损害和神经元凋亡,促进DR的发展。高糖环境下,Müller细胞功能受损,IL-17进一步加剧其功能障碍形成恶性循环。研究表明,阻断IL-17及核因子-κB激活剂1(Nuclear factor-kappa B activator 1, Act1)/肿瘤坏死因子受体关联因子6(tumor necrosis factor receptor associated factor 6, TRAF6)/核因子-κB(Nuclear factor-kappa B, NF-κB)信号通路可减轻DR的病理改变,为DR的治疗提供了新的思路。因此,深入研究IL-17与Müller细胞在DR中的相互作用机制,对于研究该疾病的发病机制及开发精准有效的治疗策略具有重要意义。
Diabetes retinopathy (DR) is a common ocular complication of diabetes, characterized by a complex pathological process involving multiple cells and inflammatory factors. Müller cells, as the primary supporting cells of the retina, not only produce interleukin-17 (IL-17) but also serve as a primary target in DR. They participate in the pathological process of DR by contributing to abnormal glutamate metabolism, increased secretion of vascular endothelial growth factor (VEGF), and regulatory functions, thereby exacerbating the inflammatory response. IL-17 is primarily secreted by T helper cell 17 (Th17) cells and enhances the inflammatory response by promoting the secretion of various inflammatory mediators (such as cytokines, chemokines, and metalloproteinases), leading to retinal microvascular damage and neuronal apoptosis, which accelerates the progression of DR. In a high-glucose environment, Müller cell function is impaired, and IL-17 further exacerbates this dysfunction, creating a vicious cycle. Studies have shown that blocking the IL-17 and Act1/TRAF6/NF-κB signaling pathways can mitigate the pathological changes associated with DR, providing new insights for the treatment of this disease. Therefore, conducting in-depth research on the interaction mechanism between IL-17 and Müller cells in DR is of great significance for exploring the pathogenesis of this disease and developing precise and effective treatment strategies.
糖尿病视网膜病变是最为常见的糖尿病微血管并发症,主要由糖尿病引起的机体代谢紊乱导致。而然在临床工作中发现,部分患者通过单纯控制血糖以延缓糖尿病视网膜病变进展,所取得效果不甚理想,一些其他因素对于糖尿病视网膜病变的发生、发展,也起到不可忽视的作用。研究表明,在并发高脂血症的糖尿病视网膜病变患者中,胆固醇代谢异常是诱发视网膜病变的主要原因之一。胆固醇代谢异常通过减弱肝脏X受体,导致胆固醇在视网膜上不断积累,降低视网膜血管内皮功能,从而造成视网膜缺血、缺氧环境的形成,又可通过增加炎症因子和细胞黏附分子-1的表达,使原本病态的糖尿病视网膜血管变得更加脆弱,该文总结了糖尿病视网膜病变的病理因素,对比分析当前糖尿病视网膜病变的主要治疗手段,通过分析胆固醇逆向转运(cholesterol reverse transport,RCT)途径转运对糖尿病视网膜病变发生、发展的影响,发现降低高血脂可提高糖尿病视网膜病变的治愈率,这将为糖尿病视网膜病变的临床防治工作提供新思路。
Diabetic retinopathy is the most common diabetic microvascular complication, which is mainly caused by metabolic disorders caused by diabetes. However, in clinical work, it is found that some patients do not achieve satisfactory results in delaying the progress of diabetic retinopathy by simply controlling blood sugar, and some other factors contribute to the occurrence and development of diabetic retinopathy. Also played a role that can not be ignored. Studies have shown that abnormal cholesterol metabolism is one of the main causes of retinopathy in diabetic retinopathy patients with hyperlipidemia. Abnormal cholesterol metabolism leads to the accumulation of cholesterol in the retina and the decrease of retinal vascular endothelial function by weakening the X receptor in the liver, resulting in the formation of retinal ischemia and hypoxia environment. it can also increase the expression of inflammatory cytokines and cell adhesion molecule-1 to make the originally morbid retinal vessels more fragile. This paper summarizes the pathological factors of diabetic retinopathy. By comparing and analyzing the main treatment methods of diabetic retinopathy at present, and by analyzing the influence of cholesterol reverse transport (cholesterolreversetransport,RCT) pathway on the occurrence and development of diabetic retinopathy, it is found that reducing hyperlipidemia can improve the cure rate of diabetic retinopathy, which will provide new ideas for the clinical prevention and treatment of diabetic retinopathy.
糖尿病视网膜病变是糖尿病引起的微血管病变之一,是不可逆性致盲的眼病。根据其病程可分为根据其病程可分为非增殖期和增殖期,其中还包括糖尿病性黄斑水肿。全科医师需要检测量裸眼视力、矫正视力和眼压,通过裂隙灯显微镜评估眼前节以及眼底检查来评估眼部整体情况。控制血糖、血压、血脂对改善预后很重要。需要重视餐前、餐后血糖,糖化血红蛋白和代谢记忆,一线降血压药物包括血管紧张素转化酶抑制剂和血管紧张素Ⅱ受体阻断剂,调脂药物首选他汀类,而非诺贝特有额外的视网膜保护作用。干预生活方式,宣教,早期发现也同样重要。全科医师需要进行眼底筛查和评分,及时转诊至眼科治疗。眼科治疗包括全视网膜激光光凝术、经平坦部玻璃体切除术、玻璃体抗血管内皮生长因子药物注射术。
Diabetic retinopathy is one of the microvascular diseases caused by diabetes, it is an irreversible blindness eye disease. According to its course, it can be divided into non-proliferative diabetic retinopathy and proliferative diabetic retinopathy, including diabetic macular edema. Te general practitioner needs to measure the uncorrected visual acuity, corrected visual acuity intraocular pressure, use the slit lamp microscope to exam the anterior segment and fundus to evaluate the overall condition of the eye. Controlling blood glucose, blood pressure and blood lipid is very important to improve the prognosis. Attach importance to pre- and postprandial blood glucose, glycosylated hemoglobin and metabolic memory should be carried out. The first-line antihypertensive drugs are angiotensin converting enzyme inhibitors and angiotensin II receptor blockers. Statins are the first choice for lipid-lowering drugs, fenofibrate has additional protective efect of retinal. Intervention in lifestyle, education and early detection are is important. Te general practitioner needs to perform fundus screening and scoring, timely refer to ophthalmology department for treatment. Ophthalmic treatment includes panretinal laser photocoagulation, pars plana vitrectomy, and intravitreal injection of anti-vascular endothelial growth factor drugs.
Diabetic retinopathy (DR), a major micro-vascular complication of diabetes, has emerged as a leading cause of visual impairment and blindness among adults worldwide. However, aside from pathological damage, the traditional laser and multi-needle operation treatments required for more advanced disease can cause further damage to the visual field and increase the operation risk. Therefore, the development of new therapeutic strategies for the prevention and treatment of DR is essential. Some emerging evidence now indicates that pigment epithelium-derived factor (PEDF), a multifunctional protein, can target multiple pathways to exert neurotropic, neuroprotective, anti-angiogenic, anti-vasopermeability, anti-inflammation, anti-thrombogenic, and anti-oxidative effects against DR. This review addresses the functions of PEDF in different pathways that could lead to potential therapeutics for the treatment of DR.
Diabetic retinopathy (DR), a major micro-vascular complication of diabetes, has emerged as a leading cause of visual impairment and blindness among adults worldwide. However, aside from pathological damage, the traditional laser and multi-needle operation treatments required for more advanced disease can cause further damage to the visual field and increase the operation risk. Therefore, the development of new therapeutic strategies for the prevention and treatment of DR is essential. Some emerging evidence now indicates that pigment epithelium-derived factor (PEDF), a multifunctional protein, can target multiple pathways to exert neurotropic, neuroprotective, anti-angiogenic, anti-vasopermeability, anti-inflammation, anti-thrombogenic, and anti-oxidative effects against DR. This review addresses the functions of PEDF in different pathways that could lead to potential therapeutics for the treatment of DR.
The purpose of this article is to report a case with rubeosis iridis treated by intravitreal aflibercept. A 61-year-old man had iris neovascularization and scanty vitreous hemorrhage secondary to proliferative diabetic retinopathy in the right eye. Neither neovascularization of angle nor elevation of intraocular pressure was found. Single intravitreal afl ibercept 2 mg injection was performed. Rubeosis iridis disappeared on the next day. Scattered retinal laser photocoagulation was added 1 week later. There was no recurrence after 3-month follow-up. Aflibercept may serve as another anti-vascular endothelial growth factor (anti-VEGF) for treating rubeosis iridis.
The purpose of this article is to report a case with rubeosis iridis treated by intravitreal aflibercept. A 61-year-old man had iris neovascularization and scanty vitreous hemorrhage secondary to proliferative diabetic retinopathy in the right eye. Neither neovascularization of angle nor elevation of intraocular pressure was found. Single intravitreal afl ibercept 2 mg injection was performed. Rubeosis iridis disappeared on the next day. Scattered retinal laser photocoagulation was added 1 week later. There was no recurrence after 3-month follow-up. Aflibercept may serve as another anti-vascular endothelial growth factor (anti-VEGF) for treating rubeosis iridis.
目的:探讨全视网膜光凝及术后应用羟苯磺酸钙治疗糖尿病视网膜病变的疗效。方法:选取96例患者,共175只眼,随机分为对照组(48例,86只眼)和研究组(48例,89只眼)。两组均予全视网膜激光光凝治疗,其中研究组术后再予羟苯磺酸钙继续12周治疗。12周后,观察两组患者治疗前后视力、血液流变学的变化。结果:治疗后研究组在视力>1.0范围的患者明显多于对照组(χ2=6.779,P=0.009), 而2组在视力≤0.4,0.4~0.6,0.7~1.0范围患者视力差异比较分别为( χ2=0.003,P=0.955),(χ2=1.640,P=0.200),(χ2=2.148,P=0.143)。治疗后研究组患者的血浆粘度、红细胞压积、红细胞变形指数、纤维蛋白原改善均优于对照组(P<0.05)。研究组总有效率89.9%,对照组75.6%,两组差异比较(χ2 =6.302,P=0.012)。结论:全视网膜激光光凝及术后应用羟苯磺酸钙治疗糖尿病性视网膜病,能有效提高视力及临床疗效,可能与改善患者血液流变相关。
Objective: To investigate the curative effect of the postoperative retinal laser photocoagulation and calcium dobesilate in the treatment of diabetic retinopathy. Methods: Selected 96 patients, 175 eyes, randomly divided into control group (48 cases, 86 eyes) and study group (48 cases, 89 eyes). Two groups were all given retinal laser photocoagulation treatment, while the study group continued to receive calcium dobesilate for 12 weeks after treatment. After 12 weeks, observed the eyesight, change of blood rheology of the two groups. Results: After the treatment, the patients with vision >1.0 in the study group were significantly more than the control group (χ2 =6.779, P=0.009), in the vision range of ≤0.4, 0.4~0.6, 0.7~1.0, the difference between the two groups was (χ2 =0.003, P=0.955), (χ2 =1.640, P=0.200), (χ2=2.148, P=0.143), respectively. After treatment, plasma viscosity, erythrocyte deposited, erythrocyte deformation index, fibrinogen in the study group were better than those in the control group (P<0.05). The total effectiveness in the study group was 89.9%, in the control group was 75.6%, the difference was statistically significant (χ2=6.302, P=0.012). Conclusion: The whole retinal laser photocoagulation and postoperative application of calcium dobesilate in treating the diabetic retinopathy can effectively improve eyesight and clinical curative effect, which may be associated with improving blood rheology.
目的:探讨基质金属蛋白酶-3(matrix metalloproteinases-3,MMP-3)基因多态位点与承德地区人群2型糖尿病视网膜病变的遗传易感性的关系。方法:应用病例对照研究方法,选取195例糖尿病视网膜病变患者(DR组),其中非增殖性糖尿病视网膜病变(non-proliferative diabetic retinopathy,NPDR)组(n=152)和增殖性糖尿病视网膜病变(proliferative diabetic retinopathy,PDR)组(n=43),205例单纯糖尿病患者(DM组)和261例正常对照组(Control组),采用限制性片段长度多态性(restrictive fragment length polymorphism,RFLP)-聚合酶链反应(polymerase chain reaction,PCR)方法检测MMP-3的基因多态性。结果:MMP-3-1171 5A/6A的等位基因及基因型频率分布在Control组,DM组和DR组之间差异无显著性(P=0.474和P=0.407)。MMP-3-1171 5A/6A的等位基因及基因型频率分布在NPDR和PDR组之间差异无显著性(P=0.724和P=0.820)。结论:MMP-3-1171 5A/6A基因多态性与2型糖尿病视网膜病变的遗传易感性无关。
目的:探讨基质金属蛋白酶-3(matrix metalloproteinases-3,MMP-3)基因多态位点与承德地区人群2型糖尿病视网膜病变的遗传易感性的关系。方法:应用病例对照研究方法,选取195例糖尿病视网膜病变患者(DR组),其中非增殖性糖尿病视网膜病变(non-proliferative diabetic retinopathy,NPDR)组(n=152)和增殖性糖尿病视网膜病变(proliferative diabetic retinopathy,PDR)组(n=43),205例单纯糖尿病患者(DM组)和261例正常对照组(Control组),采用限制性片段长度多态性(restrictive fragment length polymorphism,RFLP)-聚合酶链反应(polymerase chain reaction,PCR)方法检测MMP-3的基因多态性。结果:MMP-3-1171 5A/6A的等位基因及基因型频率分布在Control组,DM组和DR组之间差异无显著性(P=0.474和P=0.407)。MMP-3-1171 5A/6A的等位基因及基因型频率分布在NPDR和PDR组之间差异无显著性(P=0.724和P=0.820)。结论:MMP-3-1171 5A/6A基因多态性与2型糖尿病视网膜病变的遗传易感性无关。
目的:研究增殖性糖尿病视网膜病变患者玻璃体基质细胞衍生因子(Strmalcell-derivedfactor-1, SDF-1)和血管内皮生长因子(Vascular endothelial growth factor, VECF)的浓度,及其相互作用关系。方法:酶联免疫吸附法(Enzyme-linked immunosorbent assay, ELISA)检测玻璃体内 SDF-1 和 VEGF 的含量,每个标本重复3次。实验组为增性糖尿病视网膜病变(Proliferalive diabeticretinopathy, PDR)的住院患者30例,对照组为同期行玻璃体切除术的特发性黄斑裂孔患者12例。结果: PDR 患者玻璃体 VECF 的平均浓度为(2865.87+387.85) pg/ml,明显高于特发性黄斑裂孔组[(142.42+21.03) pg/ml,P < 0.0001]。增殖性糖尿病视网膜病变患者玻璃体 SDF-1的含量平均为(298.40+24.57) pg/ml,对照组为(86.91+15.89) pg/ml,两组的差异具有统计学意义(P < 0.0001)。在30例PDR患者玻璃体内 VEGF 和 SDF-1 的含量表现为正相关(Peanson相关系数 r=0.62,P < 0.001)。结论:增殖性糖尿病患者玻璃体 SDF-1 和 VECF 的含量均高于非糖尿病患者,提示 SDF-1 和 VEGF 共同参与了增殖性糖尿病视网膜病变患者病理性新生血管的形成过程。
Purpose: To investigate the levels of stromal cell-derived factor-1(SDF-1) andvascular endothelial growth factor (VEGF) in the vitreous of patients with proliferativediabetic retinopathy.
Methods: The levels of $DF-1 and VEGF in the vitreous of 30 eyes of 30 patients withproliferative diabetic retinopathy(PDR)and 12 eyes of 12 patients with idiopathicmacular hole (MH) were measured by enzyme-linked immunosorbent assay. Vitreousfluid samples were obtained by vitrectomy.
Resuls: The vitreous concentration of VEGF was signifcantly higher in eyes with PDR(2 865.87+387.85 pg/ml) than in eyes with idiopathic macular hole (142.42+21.03 Pgml, P< 0.000 1). The vitreous level of SDF-1 was also significantly higher in eyes withPDR (298.40+24.57 pg/ml ) than in eyes with idiopathic macular hole (86.91+15.89Pg/ml, P<0.000 1 ). The vitreous concentration of SDF-1 correlated significantly with that of VEGF in eyes with PDR( [correlation coefficient]r=0.62,P<0 .001)
Conclution: Vitreous levels of both SDF-1 and VEGF in patients with PDR aresignificantly higher than those of nondiabetic patients. SDF-1 may be correlated withVEGF in angiogenesis in PDR.