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1.
糖尿病视网膜病变引起的视力丧失目前已经引起了广泛的关注,但是由于糖尿病是一种多种机制作用的复杂疾病,对它的研究尚不清楚.本文就近期糖尿病视网膜病变中各种发病机制所致的视网膜血管和神经节细胞凋亡的有关研究做一综述.提示在糖尿病视网膜病变中各种机制均可引起视网膜血管和神经节细胞的凋亡,细胞凋亡在糖尿病视网膜病变的发生和发展中起着重要的作用.  相似文献   

2.
汪梦竹  蔡畅  刘洋  宋洪元  沈炜 《生命科学》2023,(10):1380-1387
糖尿病视网膜病变(diabetic retinopathy, DR)是糖尿病患者最常见的微血管系统并发症之一,是视力丧失的主要原因。增殖性糖尿病视网膜病变(proliferative diabetic retinopathy, PDR)是DR的终末期表现,其主要的病理生理学特征是视网膜新生血管形成(retinal neovascularization, RNV)。但PDR现有治疗方式存在局限性。外泌体作为细胞间沟通交流的重要使者,其携带的非编码RNA和生物活性蛋白质等重要信号分子,通过影响血管内皮细胞的增殖和迁移,在RNV中发挥关键作用。巨噬细胞是一种多功能调节细胞,越来越多的研究表明巨噬细胞外泌体在调控新生血管形成中起重要作用。该文就巨噬细胞外泌体在增殖性糖尿病视网膜病变形成中的作用与机制研究进展进行综述。  相似文献   

3.
糖尿病视网膜疾病是导致成年人失明的主要因素,是糖尿病的一种令人恐惧的并发症,高血糖被认为是促进其发展的主要原因。高血糖不断地破坏视网膜的微血管系统最终导致视网膜的许多代谢,结构和功能的紊乱。视网膜微血管内皮细胞在微脉管系统中形成树枝状供应视网膜神经,这些内皮细胞的解剖和生理符合重要视觉保护的营养需求[1]。一方面,内皮组织务必确保氧的供应和代谢活跃的视网膜营养供应;另一方面,内皮细胞有助于血-视网膜屏障将循环产生的毒素分子,白细胞促炎性物质排出体外来保护视网膜,这种特性也可能会引起疾病,比如:视网膜血管的渗漏和新生血管,炎性物质转移,因此,视网膜内皮细胞在视网膜缺血性病变,血管炎中起到重要作用,包括糖尿病视网膜病变和视网膜炎症或感染尤其是后葡萄膜炎。使用基因表达和蛋白质组学分析等研究方法,有助于了解这些疾病的发病机制。为了进一步开展对糖尿病视网膜疾病的研究,有必要就目前有关糖尿病视网膜病变患者微血管内皮细胞的研究进展予以综述,旨在为糖尿病视网膜病变的深入研究提供参考依据。  相似文献   

4.
新生血管生成包括血管发生和微血管生成。微血管生成也称血管新生,在胚胎发育、正常生理和病理生理过程中均发挥重要作用。近年来研究发现,肿瘤、糖尿病视网膜病变和风湿性关节炎等疾病的发生发展均与新生血管生成有关,而抑制血管生成已成为治疗这些疾病的有效策略。建立新生血管生成模型对研究该类疾病的分子机制和研发相关的治疗药物有极其重要的价值。为此,我们简要综述近年来新生血管生成模型及其应用进展。  相似文献   

5.
眼部新生血管存在于多种常见的眼病的发展过程中,对视功能危害大,是致盲的主要原因之一。包括糖尿病视网膜病变,视网膜栓塞,早产儿视网膜病变,老年性黄斑变性等眼病。由于其发病机制尚未完全清楚,因此目前仍无确切有效的药物治疗方法。内皮抑素(Endostatin,ES)是1997年首先从小鼠血管内皮瘤EOMA细胞培养上清中发现的,是胶原XⅧ的蛋白降解产物,分子质量约为20KD,为胶原XⅧC端非胶原区(NC1)内的184个氨基酸片段。ES是目前发现的最强的血管生成抑制因子,可抑制VEGF,bFGF,EGF等刺激的血管内皮细胞的增殖和迁移,诱导其凋亡,进而抑制新生血管的形成。通过抑制眼部新生血管的实验研究表明,ES是当前抗新生血管疗法中最有潜力的一种新药。本文就内皮抑素的结构特点及其对眼部新生血管的治疗研究进展作一综述。  相似文献   

6.
眼部新生血管存在于多种常见的眼病的发展过程中,对视功能危害大,是致盲的主要原因之一。包括糖尿病视网膜病变,视网膜栓塞,早产儿视网膜病变,老年性黄斑变性等眼病。由于其发病机制尚未完全清楚,因此目前仍无确切有效的药物治疗方法。内皮抑素(Endostatin,ES)是1997年首先从小鼠血管内皮瘤EOMA细胞培养上清中发现的,是胶原xⅧ的蛋白降解产物,分子质量约为20KD,为胶原xⅧc端非胶原区(NCl)内的184个氨基酸片段。ES是目前发现的最强的血管生成抑制因子,可抑制VEGF,bFGF,EGF等刺激的血管内皮细胞的增殖和迁移,诱导其凋亡,进而抑制新生血管的形成。通过抑制眼部新生血管的实验研究表明,ES是当前抗新生血管疗法中最有潜力的一种新药。本文就内皮抑素的结构特点及其对眼部新生血管的治疗研究进展作一综述。  相似文献   

7.
血管内皮细胞生长因子及临床应用策略   总被引:4,自引:0,他引:4  
血管内皮细胞生长因子(VEGF)是一种特异作用于血管内皮细胞的多功能细胞因子,它能引起血管通透性增加,引起细胞外基质成分改变,诱导血管形成,在炎症,创伤愈合,心脏缺血,动脉粥亲硬化,糖尿病性视网膜病变及肿瘤形成等与血管生成和病变有关的诸多病理过程中起重要作用。  相似文献   

8.
目的:探讨新生血管特异性结合肽GX1二聚体对视网膜新生血管生成的影响。方法:化学合成GX1二聚体、GX1单体、对照肽二聚体,通过CCK-8实验、管状结构形成实验、迁移实验研究GX1二聚体对大鼠视网膜内皮细胞(RMEC)增殖、微管形成、迁移能力的影响,流式细胞学技术分析其对细胞周期分布和凋亡的影响。结果:CCK-8结果显示,与对照肽二聚体及阴性对照组相比,100-200μM GX1二聚体及单体均可抑制RMEC增殖(P<0.05),且随着GX1二聚体及单体浓度升高,抑制作用逐渐增强,呈剂量依赖性;各浓度GX1二聚体均较单体抑制作用增强,并有统计学差异(P<0.05)。管状结构形成实验、细胞损伤迁移实验结果显示与对照肽二聚体及PBS组相比,GX1二聚体及GX1单体均可明显抑制视网膜内皮细胞管状结构的形成及迁移,且二聚体抑制作用强于单体;对照肽二聚体仅有轻微的抑制视网膜内皮细胞管状结构形成的作用,对细胞迁移无明显抑制作用。流式细胞术分析显示与对照肽及阴性对照组相比,GX1二聚体及GX1单体均可诱导细胞凋亡(P<0.05),且GX1二聚体的诱导作用强于GX1单体(P<0.05),而对细胞周期分布则无明显影响。结论:GX1二聚体和GX1单体均可抑制视网膜新生血管内皮细胞增殖、微管形成、迁移能力及诱导凋亡,且GX1二聚体较GX1单体作用增强。GX1二聚体有望代替单体成为糖尿病视网膜病变新生血管靶向治疗小肽类药物。  相似文献   

9.
钙介导的信号传递在血管生成中的作用血管生成可见于许多生理和病理情况。在生理情况下(如胚胎生长和创伤愈合),血管新生有一定的限度,处于刺激因素与抑制因素间平衡的精细调节之下;但在病理情况下(如癌症、糖尿病的视网膜病变等),血管生成过程失控,形成大量病理...  相似文献   

10.
糖尿病微血管病变严重影响了患者生活质量,是患者致死致残主要原因。微血管病变主要表现在视网膜、肾、神经、心肌组织。微血管病变的机制尚未完全清楚,近年越来越多研究发现血管内皮祖细胞(endothelial progenitor cells,EPCs)是该病发病重要原因。EPCs有分化为成熟的内皮细胞并且参与新血管形成和新生的能力。正常情况下内皮损失和EPCs对内皮的修复作用处于动态平衡状态,一旦EPCs受损,内皮损害和修复之间的平衡被打破,内皮层的完整性遭到破坏,必然参与糖尿病血管病变的发生发展。国内外大量研究证明糖尿病合并大血管病变EPCs数目功能改变,而糖尿病合并微血管病变EPCs的怎样变化?本文就EPCs与糖尿病微血管病变的关系进行系统综述。  相似文献   

11.
Diabetic retinopathy is one of the main microvascular complications of diabetes and remains one of the leading causes of blindness worldwide. Recent studies have revealed an important role of inflammatory and proangiogenic high mobility group 1 (HMGB-1) cytokine in diabetic retinopathy. To elucidate cellular mechanisms of HMGB-1 activity in the retina, we performed this study. The histological features of diabetic retinopathy include loss of blood-vessel pericytes and endothelial cells, as well as abnormal new blood vessel growth. To establish the role of HMGB-1 in vulnerability of endothelial cells and pericytes, cultures of these cells, or co-cultures with glial cells, were treated with HMGB-1 and assessed for survival after 24 hours. The expression levels of the cytokines, chemokines, and cell adhesion molecules in glial and endothelial cells were tested by quantitative RT-PCR to evaluate changes in these cells after HMGB-1 treatment. Animal models of neovascularization were also used to study the role of HMGB-1 in the retina. We report that pericyte death is mediated by HMGB-1-induced cytotoxic activity of glial cells, while HMGB-1 can directly mediate death of endothelial cells. We also found that HMGB-1 affects endothelial cell activity. However, we did not observe a difference in the levels of neovascularization between HMGB-1-treated eyes compared to the control eyes, nor in the levels of proangiogenic cytokine VEGF-A expression between glial cells treated with HMGB-1 and control cells. Our data also indicate that HMGB-1 is not involved in retinal neovascularization in the oxygen-induced retinopathy model. Thus, our data suggest that retinal pericyte and endothelial injury and death in diabetic retinopathy may be due to HMGB-1-induced cytotoxic activity of glial cells as well as the direct effect of HMGB-1 on endothelial cells. At the same time, our findings indicate that HMGB-1 plays an insignificant role in retinal and choroidal neovascularization.  相似文献   

12.
Diabetic retinopathy is the leading cause of visual dysfunction in working adults and is attributed to retinal vascular and neural cell damage. Recent studies have described elevated levels of membrane attack complex (MAC) and reduced levels of membrane associated complement regulators including CD55 and CD59 in the retina of diabetic retinopathy patients as well as in animal models of this disease. We have previously described the development of a soluble membrane-independent form of CD59 (sCD59) that when delivered via a gene therapy approach using an adeno-associated virus vector (AAV2/8-sCD59) to the eyes of mice, can block MAC deposition and choroidal neovascularization. Here, we examine AAV2/8-sCD59 mediated attenuation of MAC deposition and ensuing complement mediated damage to the retina of mice following streptozotocin (STZ) induced diabetes. We observed a 60% reduction in leakage of retinal blood vessels in diabetic eyes pre-injected with AAV2/8-sCD59 relative to negative control virus injected diabetic eyes. AAV2/8-sCD59 injected eyes also exhibited protection from non-perfusion of retinal blood vessels. In addition, a 200% reduction in retinal ganglion cell apoptosis and a 40% reduction in MAC deposition were documented in diabetic eyes pre-injected with AAV2/8-sCD59 relative to diabetic eyes pre-injected with the control virus. This is the first study characterizing a viral gene therapy intervention that targets MAC in a model of diabetic retinopathy. Use of AAV2/8-sCD59 warrants further exploration as a potential therapy for advanced stages of diabetic retinopathy.  相似文献   

13.
Diabetic retinopathy (DR) is one of the major complications of diabetes mellitus that causes diabetic macular edema and visual loss. DR is categorized, based on the presence of vascular lesions and neovascularization, into non-proliferative and proliferative DR. Vascular changes in DR correlate with the cellular damage and pathological changes in the capillaries of blood-retinal barrier. Several cytokines have been involved in inducing neovascularization. These cytokines activate different signaling pathways which are mainly responsible for the complications of DR. Recently; microRNAs (miRNAs) have been introduced as the key factors in the regulation of the cytokine expression which plays a critical role in neovascularization of retinal cells. Some studies have demonstrated that changing levels of miRNAs have essential role in the pathophysiology of vascular changes in patients with DR. The aim of this study is to identify the effects of miRNAs in the pathogenesis of DR via activating neovascularization pathways.  相似文献   

14.
The endoplasmic reticulum (ER) is the primary cellular compartment where proteins are synthesized and modified before they can be transported to their destination. Dysfunction of the ER impairs protein homeostasis and leads to the accumulation of misfolded/unfolded proteins in the ER, or ER stress. While it has long been recognized that ER stress is a major cause of conformational disorders, such as Alzheimer's disease, Huntington's disease, certain types of cancer, and type 2 diabetes, recent evidence suggests that ER stress is also implicated in many chronic inflammatory diseases. These diseases include irritable bowel syndrome, atherosclerosis, diabetic complications, and many others. Diabetic retinopathy is a common microvascular complication of diabetes, characterized by chronic inflammation, progressive damage to retinal vascular and neuronal cells, vascular leakage, and abnormal blood vessel growth (neovascularization). In this review, we discuss the role and mechanisms of ER stress in retinal inflammation and vascular damage in diabetic retinopathy.  相似文献   

15.
Diabetic retinopathy (DR) is a severe complication of diabetes and the leading cause of blindness among working adults worldwide. DR is being widely recognized as a neurodegenerative disease of the retina, since, retinal neurons are damaged soon after diabetes onset. Diabetes-induced oxidative stress is considered as central factor that dysregulates neurotrophic factors and activates apoptosis, thereby damages neurons in the diabetic retina. Flavonoids being a powerful antioxidant have been considered to protect neurons in diabetic retina. The purpose of this study was to analyze the beneficial effects of flavonoid, quercetin to protect neurons in the diabetic rat retina. We quantitated the expression levels of BDNF, NGF, TrkB, synaptophysin, Akt, Bcl-2, cytochrome c and caspase-3 using Western blotting techniques in the diabetic retina with and without quercetin treatments and compared with non-diabetic rats. In addition, we employed ELISA techniques to determine the level of BDNF. Caspase-3 activity and the level of glutathione were analyzed by biochemical methods. Our results indicate that quercetin treatment to diabetic rats caused a significant increase in the level of neurotrophic factors and inhibited the level of cytochrome c and caspase-3 activity in the diabetic retina. Furthermore, the level of an anti-apoptotic protein Bcl-2 was augmented in quercetin treated diabetic retina. Thus, quercetin, may protect the neuronal damage in diabetic retina by ameliorating the levels of neurotrophic factors and also by inhibiting the apoptosis of neurons. Therefore, this study suggests that quercetin can be a suitable therapeutic agent to prevent neurodegeneration in diabetic retinopathy.  相似文献   

16.
Angiotensin and diabetic retinopathy   总被引:2,自引:0,他引:2  
Diabetic retinopathy develops in patients with both type 1 and type 2 diabetes and is the major cause of vision loss and blindness in the working population. In diabetes, damage to the retina occurs in the vasculature, neurons and glia resulting in pathological angiogenesis, vascular leakage and a loss in retinal function. The renin-angiotensin system is a causative factor in diabetic microvascular complications inducing a variety of tissue responses including vasoconstriction, inflammation, oxidative stress, cell hypertrophy and proliferation, angiogenesis and fibrosis. All components of the renin-angiotensin system including the angiotensin type 1 and angiotensin type 2 receptors have been identified in the retina of humans and rodents. There is evidence from both clinical and experimental models of diabetic retinopathy and hypoxic-induced retinal angiogenesis that the renin-angiotensin system is up-regulated. In these situations, retinal dysfunction has been linked to angiotensin-mediated induction of growth factors including vascular endothelial growth factor, platelet-derived growth factor and connective tissue growth factor. Evidence to date indicates that blockade of the renin-angiotensin system can confer retinoprotection in experimental models of diabetic retinopathy and ischemic retinopathy. This review examines the role of the renin-angiotensin system in diabetic retinopathy and the potential of its blockade as a treatment strategy for this vision-threatening disease.  相似文献   

17.
Many growth factors are implicated in the pathogenesis of proliferative diabetic retinopathy. Alteration of growth factors and their receptors in diabetes has been shown in both experimental and clinical studies. Sustained hyperglycemia resulting from long-standing diabetes leads to several biochemical abnormalities that consequently result in retinal hypoxia. Retinal oxygenation state regulates various growth factors that promote angiogenesis in order to meet the oxygen demands of the tissue. However, unregulated expression of these growth factors and induction of complex cascades leading to augmentation of other proangiogenic factors, which may not be regulated by tissue oxygenation, leads to uncontrolled retinal neovascularization and blindness in diabetic patients.  相似文献   

18.
Diabetic retinopathy (DR) is a serious complication of diabetes contributing to blindness in patients. Inhibiting retinal neovascularization is a potent strategy for diabetic retinopathy treatment. Reportedly, the stable expression of lin-28 homolog B (LIN28B), a member of the highly conserved RNA-binding protein LIN28 family, could promote vascular endothelial growth factor (VEGF) expression; herein, we investigated the role and mechanism of LIN28B in diabetic retinopathy progression from the perspective of microRNA (miRNA) regulation. We identified miR-152 as a miRNA that may target the LIN28B 3′-untranslated region and can be significantly downregulated under high-glucose (HG) condition. The expression of miR-152 was remarkably suppressed, whereas the expression of LIN28B was significantly increased under HG condition within both human retinal endothelial cells (hRECs) and retinal microvascular endothelial cell line (hRMECs). miR-152 overexpression significantly suppressed, while LIN28B overexpression promoted the angiogenesis and the protein levels of proangiogenesis factors in both hRECs and hRMECs. More importantly, LIN28B overexpression could remarkably attenuate the effect of miR-152 overexpression. In summary, miR-152 overexpression could inhibit HG-induced angiogenesis in both hRECs and hRMECs via targeting LIN28B and suppressing VEGF signaling. Further, in vivo experiments are needed for the application of miR-152/LIN28B axis in the treatment for diabetic retinopathy.  相似文献   

19.
Diabetic retinopathy represents the most common causes of vision loss in patients affected by diabetes mellitus. The cause of vision loss in diabetic retinopathy is complex and remains incompletely understood. One of the earliest changes in the development of retinopathy is the accelerated apoptosis of retinal microvascular cells and the formation of acellular capillaries by unknown mechanism. Results of a recent research suggest an important role of matrix metalloproteinases (MMPs) in the development of diabetic retinopathy. MMPs are a large family of proteinases that remodel extracellular matrix components, and under pathological condition, its induction is considered as a negative regulator of cell survival; and in diabetes, latent MMPs are activated in the retina and its capillary cells, and activation of MMP-2 and -9 induces apoptosis of retinal capillary cells. This review will focus on the MMP-2 and MMP-9 in the diabetic retina with special reference to oxidative stress, mitochondria dysfunction, inflammation and angiogenesis, as well as summarizing the current information linking these proteins to pathogenesis of diabetic retinopathy.  相似文献   

20.
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