血管内皮生长因子与糖尿病视网膜病

糖尿病视网膜病是进展性微血管病变,而血管内皮生长因子(VEGF)是内皮细胞特异性促有丝分裂原,具有促进内皮细胞增殖、增加微血管通透性、诱导血管生成等多种功能,可调节内皮细胞外基质溶解、内皮细胞迁移、增生和管腔形成,参与生理过程的血管形成。VEGF能诱导视网膜血管闭塞,引起视网膜缺血。VEGF抑制剂以及VEGF信号转导通路抑制剂的研究及其应用,将为糖尿病视网膜病变的诊断和治疗提供广阔的前景。     

血管内皮生长因子与糖尿病视网膜病

糖尿病视网膜病是进展性微血管病变，而血管内皮生长因子(VEGF)是内皮细胞特异性促有丝分裂原，具有促进内皮细胞增殖、增加微血管通透性、诱导血管生成等多种功能，可调节内皮细胞外基质溶解、内皮细胞迁移、增生和管腔形成，参与生理过程的血管形成。VEGF能诱导视网膜血管闭塞，引起视网膜缺血。VEGF抑制剂以及VEGF信号转导通路抑制剂的研究及其应用，将为糖尿病视网膜病变的诊断和治疗提供广阔的前景。     

糖尿病视网膜病变的治疗进展

严格的血糖、血压控制和激光光凝术是治疗和预防糖尿病视网膜病变,减少失明的主要措施。蛋白激酶C(PKC)-β抑制剂和肾素—血管紧张素系统抑制剂通过下调血管内皮生长因子发挥作用,其疗效被越来越多的临床证据所证明,特别是PKC-β抑制剂ruboxistaurin。此外,生长抑素类似物、皮质醇类玻璃体内注射的疗效也较明显,但还需进一步研究证实。晚期糖基化终末产物抑制剂、噻唑烷二酮类、他汀类药物对糖尿病视网膜病变的治疗也有一定作用。     

蛋白激酶C-β及其抑制剂与糖尿病视网膜病变

糖尿病视网膜病变的生化机制之一是高糖诱导的蛋白激酶C-β活化导致细胞信号的改变.经典的蛋白激酶C-β活化主要是二酰基甘油释放增加及多种致炎细胞因子参与的结果.近年的实验室研究及临床研究报道显示,ruboxistanrin是一种蛋白激酶C-β抑制剂,可预防糖尿病视网膜病变及糖尿病黄斑水肿的进展.本文就蛋白激酶C-β与糖尿病视网膜病变的发生及其抑制剂ruboxistaurin对糖尿病视网膜病变的治疗机制、疗效、安全性及前景进行综述.     

糖尿病患者视网膜中央动脉血流动力学与糖化血红蛋白关系的探讨

糖尿病视网膜病变 (DR)是糖尿病患者致盲的主要的原因 ,高血糖是导致糖尿病微血管病变的主要原因 ,而糖尿病视网膜病变的进展与微血管血流动力学改变及视网膜缺血缺氧密切相关。通过彩色多普勒超声检测糖尿病患者视网膜中央动脉 (CRA) ,分析其血流动力学改变与糖化血红蛋白水平变化之间的关系 ,旨在探讨糖尿病视网膜血流变化的规律及影响因素 ,为防治糖尿病视网膜病变提供理论依据。一、资料与方法1.对象 :糖尿病组 :系本院按 WTO标准确诊 2型糖尿病6 6例 (132眼 ) ,并排除有关药物如 :血管紧张素转换抑制剂、芦丁类药物的应用及伴有其…     

视网膜Müller细胞在糖尿病视网膜病变发病中的作用及其研究进展

糖尿病视网膜病变（DR）是糖尿病的重要并发症,其发病机制尚未完全明了。以往对DR的研究主要关注其血管病变,而近年来研究表明,在DR的视网膜血管病变发生之前,已有视网膜神经变性,包括视网膜神经元及神经胶质细胞的变性及丢失。Müller细胞作为视网膜最主要的神经胶质细胞,分布于整个视网膜,包绕视网膜上各级神经元的胞体、突起及视网膜血管。Müller细胞不但可以影响视网膜血管的病变,还能影响视网膜神经细胞的病变,     

细胞因子与糖尿病视网膜病

糖尿病视网膜病变,尤其是增殖型病变,以视网膜新生血管和纤维化为特征,其发生发展与细胞增殖调控失常有关。成纤维细胞生长因子、血管内皮生长因子、转化生长因子、胰岛素样生长因子、肿瘤坏死因子等细胞因子与视网膜多种细胞的生长、增殖有密切联系。研究细胞因子与糖尿病视网膜病变发生、发展的关系,为糖尿病视网膜病变的治疗、监测提供了一个新的理论依据。     

细胞因子与糖尿病视网膜病

糖尿病视网膜病变,尤其是增殖型病变,以视网膜新生血管和纤维化为特征,其发生发展与细胞增殖调控失常有关。成纤维细胞生长因子、血管内皮生长因子、转化生长因子、胰岛素样生长因子、肿瘤坏死因子等细胞因子与视网膜多种细胞的生长、增殖有密切联系。研究细胞因子与糖尿病视网膜病变发生、发展的关系,为糖尿病视网膜病变的治疗、监测提供了一个新的理论依据。     

糖尿病患者荧光素眼底血管造影分析

目的对糖尿病患者应用荧光素眼底血管造影的结果进行分析,并对于应用于诊断糖尿病视网膜病变的临床价值进行分析。方法选取于2014年5月—2016年4月期间在该院就诊的糖尿病患者150例(264眼),对以上患者均分别进行检眼镜检查以及荧光素眼底血管造影,并对两种不同检查方式的结果进行对照研究。结果荧光素眼底血管造影诊断视网膜病变的病变率明显高于检眼镜检查[90.15%VS 68.94%],其中非增生性糖尿病性视网膜病变、增生前糖尿病性视网膜病变、增生型糖尿病性视网膜病、糖尿病性黄斑病变、糖尿病性视神经乳头病变分别占比21.85%、28.99%、26.05%、13.87%、9.24%。结论荧光素眼底血管造影应用于糖尿病患者视网膜病变中具有显著的临床诊断价值,值得大力推广。     

瘦素与糖尿病视网膜病变有关

在糖尿病视网膜病变的进展阶段,新生血管形成的机制尚不明确。最近的研究发现,瘦素在体外具有血管生成的作用,且在体内诱导新生血管形成。本研究的目的是探讨血浆瘦素水平与糖尿病视网膜病变严重程度的关系。对象与方法　受试者为70例仅接受磺脲类药物治疗的2型糖尿病患者,另有66例年龄、体重指数和性别与之相匹配的健康志愿者做为对照。受试者进行眼底镜的检查和眼底荧光血管造影,根据视网膜病变的阶段分为3个亚组:无视网膜病变组33例(女23,男10),非增殖性糖尿病视网膜病变组(ＮＰＤＲ)20例(女13,男7),增殖性糖尿病视网膜病变组(ＰＤＲ)17…     

Sight-threatening retinopathy is associated with lower mortality in type 2 diabetic subjects: a 10-year observation study

AIMS: To study associations between diabetic retinopathy and development of stroke, myocardial infarction and death in type 2 diabetic patients. METHODS: During a 10-year observation period, 363 type 2 diabetic patients (diagnosis > or =30 years of age) attending an outpatient clinic were studied regarding the prevalence and incidence of retinopathy and associated risk factors, i.e., (HbA(1c), blood pressure, albuminuria, plasma creatinine, age, sex and diabetes duration) in relation to the development of myocardial infarction, stroke and death. The degree of retinopathy was classified as no retinopathy, background or sight-threatening retinopathy, i.e., clinically significant macular edema, severe non-proliferative or proliferative retinopathy. RESULTS: During the study period, 62 patients had had myocardial infarction, 54 stroke and 99 patients died. Patients with sight-threatening retinopathy at baseline (n=41) had a 2.2-fold increased (p<0.01) risk for death compared to patients with no or background retinopathy, even when controlled for medical risk factors. When adjusted for medical risk factors, patients with no retinopathy at baseline (n=226) who remained without retinopathy or developed background retinopathy (n=187) during the study period, had a 3.6-fold increased risk for death (95% CI, 1.1, 11.8), (p=0.03), compared to patients who developed sight-threatening retinopathy (n=39), while the incidence of myocardial infarction did not differ. More patients who developed sight-threatening retinopathy were treated with ACE inhibitors than patients who did not (41% versus 24%; p=0.03). CONCLUSION: Despite more medical risk factors, patients who developed sight-threatening retinopathy had lower mortality compared to patients with no or background retinopathy at follow-up. More patients who developed sight-threatening retinopathy were treated with ACE inhibitors but this seemed not to have influenced the lower mortality rate in this group, whereas the use of ACE inhibitors in patients who did not develop sight-threatening retinopathy was connected with lower mortality rate.     

Pharmacological treatment of diabetic retinopathy

Diabetic retinopathy is the most serious diabetic complication. Modern pharmacotherapy offers a wide range of potential treatments (ACE inhibitors, sartans, hypolipidemic drugs, drugs influencing proteinkinase C and vascular endotelial growth factor etc.). Diabetic retinopathy was previously treated surgically but today pharmacotherapy is becoming increasingly important. Undoubtly basic strategy for preventing diabetic retinopathy is antihyperglycemic therapy and normoglycemia.     

Calcium Dobesilate in the Treatment of Diabetic Retinopathy

The incidence of diabetic retinopathy is still increasing in developed countries. Tight glycemic control and laser therapy reduce vision loss and blindness, but do not reverse existing ocular damage and only slow the progression of the disease. New pharmacologic agents that are currently under development and are specifically directed against clearly defined biochemical targets (i.e. aldose reductase inhibitors and protein kinase C-beta inhibitors) have failed to demonstrate significant efficacy in the treatment of diabetic retinopathy in clinical trials. In contrast, calcium dobesilate (2,5-dihydroxybenzenesulfonate), which was discovered more than 40 years ago and is registered for the treatment of diabetic retinopathy in more than 20 countries remains, to our knowledge, the only angioprotective agent that reduces the progression of this disease. An overall review of published studies involving calcium dobesilate (CLS 2210) depicts a rather 'non-specific' compound acting moderately, but significantly, on the various and complex disorders that contribute to diabetic retinopathy. Recent studies have shown that calcium dobesilate is a potent antioxidant, particularly against the highly damaging hydroxyl radical. In addition, it improves diabetic endothelial dysfunction, reduces apoptosis, and slows vascular cell proliferation.     

Prospects for angiotensin receptor blockers in diabetic retinopathy

Retinopathy is the most common microvascular complication of diabetes mellitus, and is an important cause of blindness worldwide. Clinical trials have demonstrated that tight metabolic control inhibits the progression of retinopathy. Good blood pressure control has been shown to be protective in type 2 diabetes, and it may also reduce proliferative retinopathy in type 1 diabetes. However, such control is often difficult to achieve in clinical practice, and may be associated with problems such as hypoglycaemia. New therapies are therefore needed to reduce the risk of retinopathy. There is growing evidence that the renin-angiotensin system (RAS) plays an important role in the pathogenesis of diabetic retinopathy, and this has led to interest in RAS inhibitors as agents to prevent retinopathy. Several trials have suggested that ACE inhibitor therapy can inhibit progression of retinopathy. The Diabetic Retinopathy Candesartan Trials (DIRECT) Programme is currently investigating the effects of the angiotensin II receptor blocker candesartan on the incidence of retinopathy in type 1 diabetes and its progression in type 1 and type 2 diabetes. It is hoped that the results from such large-scale clinical trials will provide more specific information about the medical treatment of diabetic retinopathy.     

Pharmacological approach to diabetic retinopathy

Diabetic retinopathy is the most frequent cause of legal blindness in the population of 30-to-70-year olds. Whether retinopathy appears or not depends mainly on the duration of the disease and the degree of metabolic control the patient maintains. High blood glucose values lead to important changes in cellular metabolism and the main effects of these alterations are endothelial dysfunction that sets in motion the morphological process of diabetic retinopathy. The biochemical lesions caused by prolonged hyperglycemia can be positively influenced, but usually not normalized, pharmacologically with some groups of drugs, which are now under development. This makes tight control of glycemia a key measure in preventing the onset or progression of diabetic retinopathy, together with an effective program of ophthalmologic detection and follow-up in patients with diabetes. Regarding the role of endothelial dysfunction, antiplatelet drugs have been shown to slow some aspects of the evolution of diabetic retinopathy in its initial stages, mainly a lower degree of microaneurysms. However, a new approach to controlling endothelial dysfunction shows promise, mainly through the vascular endothelial growth factor (VEGF) inhibitors. These agents may prove to be especially useful in the treatment of proliferative diabetic retinopathy. Other encouraging results have been obtained in studies of antioxidant drugs and inhibitors of the formation of advanced glycation end products. Once retinal lesions appear, preventive measures need to be redoubled, with special attention to controlling glycemia; however, it is also necessary to resort to laser photocoagulation. This intervention aims to eliminate areas of ischemia and to diminish the formation of retinal exudates. If this measure fails or if vitreous hemorrhage appears, the only remaining therapeutic measure is vitrectomy.     

Diabetische Retinopathie und Makulopathie

Diabetic retinopathy is the most frequent microvascular complication in diabetes. Its early development indicates an increased cardiovascular risk. Since the early stages lack symptoms, yearly screening intervals are mandatory. Each retinopathy level determines evidence-based treatment with mutual interactive contributions from diabetology and ophthalmology. Intravitreal injection of inhibitors of the vascular endothelial growth factor may improve the so far only modestly successful therapy of diabetic macular edema.     

Medical management of diabetic retinopathy.

Although current treatment and prevention of diabetic retinopathy with laser photocoagulation, and tight metabolic and blood pressure control has reduced the risk of visual loss, there is still a need for additional therapies. A literature review on medical therapies for diabetic retinopathy has been performed, and the following classes of drugs are discussed: blockers of the renin-angiotensin system, protein kinase C-beta inhibitors, glitazones, somatostatin analogues, lipid-lowering drugs and anti-inflammatory drugs. There is experimental and clinical data suggesting beneficial effect from several classes of drugs on diabetic retinopathy, and results from large clinical trials are awaited within the next 3-4 years.     

Diabetic Retinopathy: An Update on Treatment

Diabetic retinopathy is a progressive disease that results from vascular injury due to chronic hyperglycemia. It is the leading cause of blindness in working-age adults in the US and is usually asymptomatic until late stages. Treatment with laser photocoagulation is effective at preventing severe vision loss; thus, diabetic patients should be referred for regular screening by an ophthalmologist. New inhibitors of vascular endothelial growth factor may provide targeted nonsurgical treatment to improve vision in diabetic retinopathy.     

Diabetic retinopathy: pathogenesis,clinical grading,management and future developments

Decades of research into the pathophysiology and management of diabetic retinopathy have revolutionized our understanding of the disease process. Diabetic retinopathy is now more accurately defined as a neurovascular rather than a microvascular disease as neurodegenerative disease precedes and coexists with microvascular changes. However, the complexities of the pathways involved in different stages of disease severity continue to remain a challenging issue for drug discovery. Currently, laser photocoagulation is the mainstay of treatment for proliferative diabetic retinopathy, but is gradually being superseded for diabetic macular oedema. However, it is destructive and at best results in a gradual but modest improvement in vision in the long term. So, diabetic retinopathy remains the most prevalent cause of visual impairment in the working‐age population despite established screening programmes, early diagnosis and treatment of the condition. The recent discovery of inhibitors of vascular endothelial growth factor is revolutionizing the management of diabetic retinopathy, particularly diabetic macular oedema. However, not all patients respond to anti‐vascular endothelial growth factor agents, reinforcing the fact that diabetic retinopathy is a multifactorial disease. Studies are still required to improve our understanding of how retinal structure correlates with visual function. It is hoped that these will lead to better characterization of the disease phenotype based on treatment responses to different agents and allow an algorithm to be developed that will guide the management of diabetic retinopathy and diabetic macular oedema at different stages of severity.     

Resting Heart Rate Is Associated With Nonproliferative Retinopathy in Normoalbuminuric Type 1 Diabetic Patients

Previous studies have reported that retinopathy might be already present in the normoalbuminuric state in type 1 diabetic patients. The aim of this study was to evaluate the prevalence and predictors of nonproliferative retinopathy in normoalbuminuric type 1 diabetic patients. The study included 312 normoalbuminuric type 1 diabetic patients with normal renal function before any interventions with statins, angiotensin‐converting enzyme inhibitors, or angiotensin II receptor blockers. Diagnosis of nonproliferative retinopathy was made by fundoscopy after pupillary dilatation. Urinary albumin excretion (UAE) rate was measured from at least two 24‐hour urine samples. Nonproliferative retinopathy was present in 36% of normoalbuminuric patients. Patients with nonproliferative retinopathy were older and had longer duration of diabetes, higher hemoglobin A_1c, daily insulin dose, and higher resting heart rate (RHR) (P≤.01 for all). Patients in the 4th quartile of RHR were older and had longer duration of diabetes, higher hemoglobin A_1c, daily insulin dose, serum creatinine, UAE, and a significantly higher prevalence of nonproliferative retinopathy compared with subjects in the 2nd, 3rd, and 4th quartiles (P<.05). In logistic regression analysis, after adjustment for risk factors, higher RHR was significantly associated with risk of nonproliferative retinopathy in patients (P<.001), with odds ratios of 1.02 to 1.08. These data suggest that RHR is independently associated with nonproliferative retinopathy in normoalbuminuric type 1 diabetic patients.