烟草烟雾与老年性黄斑变性

老年性黄斑变性（AMD）与年龄、营养、免疫、烟草烟雾等因素有关。烟草烟雾可促进脉络膜新生血管（CNV）形成，诱发AMD。烟草烟雾中的主要生物碱尼古丁通过与视网膜色素上皮细胞中烟碱胆碱受体结合从而影响血浆中血管内皮生长因子与色素上皮衍生因子的比率；收缩视网膜血管，导致缺血缺氧；烟草烟雾中的自由基或间接消耗抗氧化剂诱发氧化应激及苯并芘对视网膜的毒性作用等。在预防CNV形成、控制AMD发生中，烟草烟雾是为数不多的可确定且可预防的环境因素。充分认识吸烟与CNV以及AMD的关系，对于AMD的早期预防、探索新的治疗途径有着重要的意义。     

老年黄斑变性的药物治疗

在美国等发达国家中，老年黄斑变性(AMD)是65岁以上人群最主要的致盲原因。迄今为止，老年黄斑变性的治疗方法很有限。目前的治疗方法可以分为两大类：物理治疗和药物治疗。前者曾受到广泛关注却效果不显著，而后者近来发展迅速。药物治疗包括：光动力学治疗、激素、血管内皮生长因子VEGF的抑制药物、细胞外间质的修饰药物、基因治疗、营养补充和脉络膜血流促进药物等。光动力学治疗是某些特定类型的新生血管型AMD唯一有效的治疗方法。Anecortave acetate(一种人工合成的激素)球旁注射可以稳定患者的视力达6mo。玻璃体腔注射VEGF的拮抗药物，也能稳定患者的视力3mo。在AMD的早期就可发现脉络膜血流的改变。血管压力的增加是AMD重要的血流动力学改变，它导致了脉络膜毛细血管血流减少。经过一系列反应，最终导致视网膜色素上皮细胞变性、Bruch膜断裂、脉络膜新生血管形成、老年黄斑变性、失明。因此改善脉络膜血流的药物可能阻止AMD的发展和恶化。虽然这些药物还多处于试验阶段，但还是很有希望来发现治疗AMD的药物，从而阻止其发展。     

年龄相关性黄斑变性发病机制研究热点：血管模式[英]／Friedman E…／／Br J Ophthalmol.

年龄相关性黄斑变性(AMD)血管模式的确立，基于AMD与动脉粥样硬化有共同的风险因素和发病机制。该模式认为AMD是视网膜色素上皮(RPE)、脉络膜灌注损坏的血管病变。其发病机制为：(1)由于脂质进行性浸润，眼组织顺应性降低，脉络膜血管阻力增加。随年龄增长，黄斑区脉络膜毛细血管进行性变窄，亦促使阻力增强。     

年龄相关性黄斑变性发病机制研究热点:血管模式

年龄相关性黄斑变性(AMD)血管模式的确立,基于AMD与动脉粥样硬化有共同的风险因素和发病机制。该模式认为AMD是视网膜色素上皮(RPE)、脉络膜灌注损坏的血管病变。其发病机制为:(1)由于脂质进行性浸润,眼组织顺应性降低,脉络膜血管阻力增加。随年龄增长,黄斑区脉络膜毛细血管进行性变窄,亦促使阻力增强。(2)体循     

吸烟与年龄相关性黄斑变性

吸烟是年龄相关性黄斑变性（AMD）最重要和唯一公认的可修正危险因素。吸烟可增加AMD的患病风险,促进病变发展,而且与一些遗传易感因素可能具有联合作用。其作用机制包括影响血流动力学、氧化损伤和促进新生血管形成等。吸烟在AMD发生发展中的重要作用使其成为AMD防治研究中关注的焦点之一。     

MMP-2和MMP-9在脉络膜新生血管膜的表达

目的　研究年龄相关性黄斑变性 (age relatedmaculardegeneration ,AMD)脉络膜新生血管膜基质金属蛋白酶 (matrixmetalloproteinases,MMPs)的表达 ,探讨MMP 2和MMP 9在AMD脉络膜新生血管膜形成过程中的作用。方法　实验组标本取自AMD患者经扁平部玻璃体切割术和视网膜下膜取出术获得的脉络膜新生血管膜 17例 ,免疫组织化学法检测MMP 2和MMP 9的表达。结果　 17例AMD脉络膜新生血管膜MMP 2和MMP 9表达阳性 ,正常人视网膜无MMP 2和MMP 9表达。结论　AMD脉络膜新生血管膜有MMP 2和MMP 9的表达 ,MMP 2和MMP 9可能通过降解Bruch膜 ,促进脉络膜新生血管在视网膜色素上皮下生长 ,参与AMD的病理变化过程。     

老年性黄斑变性和息肉状脉络膜血管病变

老年性黄斑变性(age-relatedmaculardegeneration,AMD)根据病理和临床表现分为萎缩型(atrophicsenilemaculardegeneration)和渗出型(exudativesenilemaculardegeneration)。萎缩型AMD主要为脉络膜毛细血管萎缩、玻璃膜增厚和视网膜色素上皮萎缩等所致的黄斑区萎缩变性;渗出型AMD主要为玻璃膜破坏、脉络膜血管侵入视网膜下形成新生血管,导致视网膜和/或色素上皮有浆液和/或出血[1]。以往息肉状脉络膜血管病变(polypoidalchoroidalvasculopathy,PCV)在诊断和治疗方面与渗出型AMD无明确区别,1990年Yannuzzi等[2]对该病进行了描述,因发病…     

内质网应激在年龄相关性黄斑变性中的作用

内质网是哺乳动物细胞内蛋白质加工的重要细胞器,各种因素导致的内质网应激(ERS)过强均可能损伤细胞功能,甚至引起细胞死亡.年龄相关性黄斑变性(AMD)是多因素导致的常见致盲性疾病,研究证实氧化应激、炎症反应及脂代谢异常等因素引起的ERS在AMD的发生发展过程中起重要作用,其中促使视网膜色素上皮(RPE)中血管内皮生长因子(VEGF)表达上调,进而促进脉络膜新生血管(CNV)长入Bruch膜而形成CNV膜是干性AMD转变为湿性AMD的主要病理机制.就ERS的发生过程、发生机制及氧化应激、炎症反应等因素与ERS在AMD病变过程中的相互作用进行综述.     

年龄相关性黄斑变性合并视网膜色素上皮脱离的诊治

视网膜色素上皮脱离(PED)是视网膜色素上皮的基底膜与Bruch膜之间的分离。渗出性年龄相关性黄斑变性(e AMD)合并PED,可表现为有脉络膜新生血管的存在。在脉络膜新生血管的形成中,血管内皮生长因子(VEGF)起着重要作用。所以抗VEGF治疗已成为目前AMD防治的一个研究热点。本文对AMD合并PED的分类和治疗进展综述如下。     

光动力学疗法在老年黄斑变性中的应用

年龄相关性黄斑变性 (age- related maculardegeneration,AMD)是老年人致盲眼病中最常见的原因之一 ,近年以光动力学疗法 (phothdynamictherapy,PDT)选择性治疗 AMD引起的脉络膜新生血管 (choroidal neovascularization,CNV)广受重视。本文对此作一综述。AMD在西方国家是导致 65岁以上老年人视力下降的首要原因。萎缩型 AMD病人视力会逐步下降 ,其中血管化 AMD约占 1 0 % ,经常导致视力急剧丧失〔1〕。有人报道 65岁以上老年人 1 .7%一只眼有血管化 AMD〔2〕。如果另外一眼出现大的玻璃膜疣或局部色素增殖 ,则很有可能也演变为血…     

炎症与年龄相关性黄斑变性

年龄相关性黄斑变性(AMD)是中老年人常见的致盲性眼病之一,特征性改变是玻璃膜疣(drusen)形成和脉络膜新生血管(CNV),确切发病机制不清,衰老、营养失衡和遗传等多种因素参与其发病。近年来研究发现机体慢性炎症和补体活化等免疫机制在其发病中占有重要作用,从AMD患者病灶组织及玻璃膜疣中发现有巨噬细胞和补体成分沉积,玻璃膜疣的形成与补体成分在Bruch膜上的活化以及脉络膜巨噬细胞吞噬功能下调有关,CNV的形成与补体成分活化、炎症刺激以及脉络膜巨噬细胞聚集活化有关,补体因子H的基因多态性也与AMD的发生有关。脂褐素碎片可刺激视网膜色素上皮细胞活化并分泌炎性细胞因子或血管生长因子,促进CNV的形成;长期光氧化损伤可导致视网膜蛋白变性形成新抗原,并刺激机体产生自身抗体,导致补体活化和巨噬细胞聚集,参与玻璃膜疣的形成和CNV发生。综上证据表明慢性炎症和补体活化等免疫学改变在AMD发生中起着重要作用,这就提示抗炎治疗可作为AMD患者的有效辅助治疗措施。     

Nicotine increases size and severity of experimental choroidal neovascularization

PURPOSE: Cigarette smoking is the strongest environmental risk factor for all forms of age-related macular degeneration (AMD). In the present study, the influence of nicotine on the severity of choroidal neovascularization (CNV) in a mouse model of neovascular AMD and its effects on vascular smooth muscle cells derived from mouse choroid were investigated. METHODS: A mouse model for CNV was used to study the effects of nicotine in young and middle-aged mice. Nicotine was administered orally in the drinking water to achieve serum levels consistent with those of chronic smokers. Hexamethonium, a nonspecific nicotinic receptor antagonist, was injected subconjunctivally to counteract the effects of nicotine. A mouse choroidal vascular smooth muscle cell line was exposed to nicotine, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), or a combination of one of the factors and nicotine. Cell growth was determined by cell counts, and the activity of matrix metalloproteinase (MMP)-2 and -9 was quantified by gel zymography. RESULTS: Nicotine administration resulted in increased size and vascularity of CNV, and older mice developed a greater relative increase than younger mice. This effect was blocked by subconjunctival hexamethonium. Choroidal vascular smooth muscle cells demonstrated a statistically significant increase in growth after exposure to a combination of PDGF and nicotine. Nicotine also reversed VEGF-induced suppression of MMP-2 activity. CONCLUSIONS: Nicotine increases size and severity of experimental CNV in the present mouse model, possibly by potentiating PDGF-mediated upregulation of proliferation of choroidal smooth muscle cells or by other mechanisms. These results suggest that non-neuronal nicotinic receptor activation probably mediates some of the harmful effects of cigarette smoking in wet AMD.     

Effect of Quercetin on Formation of Choroidal Neovascularization (CNV) in Age-related Macular Degeneration(AMD)

Purpose: Age-related macular degeneration (AMD) as a disease entity is "dry" at early stage and made up of two main components at late stage:atrophic AMD and exudative AMD. Quercetin acts as an anti-oxidant to protect retinal pigment epithelial cells (RPE) from damaged by oxidative stress, but its effect on formation of choroidal neovascularization (CNV)in AMD is unclear. The aim of this study is to investigate the effect of quercetin on the formation of CNV in AMD. Methods:The development of CNV induced by laser was detected by fluorescein angiography (FA). Colored microsphere technique was used to determine the choroidal blood flow in ocular hypertensive rabbit eyes.In in vitro studies, HUVECs were treated with NaIO3, H2O2 and NaN3 to induce oxidative cell damages. The effect of quercetin on various oxidationsinduced injuries in HUVECs was measured by MTT assay. HUVECs migration was assessed using a wound healing assay. Results:Quercetin significantly inhibited the formation of laser-induced CNV.The choroidal blood flow in rabbit eyes was significantly increased after quercetin instillation. In vitro results showed quercetin enhanced various oxidations-induced injuries in HUVECs and inhibited migration of HUVECs during wound healing. Conclusion: Quercetin inhibited the formation of CNV both in vivo and in vitro and increased choroidal blood flow.It could become a promising candidate for the treatment of AMD.     

Molecular mechanism of choroidal neovascularization in age-related macular degeneration

The exudative form of age-related macular degeneration (AMD) is characterized by choroidal neovascularization (CNV). Retinal pigment epithelial cells (RPE) secrete various angiogenesis-related factors, especially vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF). The imbalance between the VEGF and PEDF secreted by RPE is a key contributor to the development of CNV in AMD. The earliest clinical hallmark of AMD is the presence of drusen. Although drusen are an epidemiological risk factor for the development of CNV, the mechanism of how drusen induce the development of CNV remains unclear. Recent proteome analysis demonstrated that amyloid beta (Abeta) deposition was specific to drusen from eyes with AMD. We focused on Abeta and investigated the effect of Abeta on cultured human RPE cells as well as ocular findings in neprilysin gene-disrupted mice, which leads to an increased deposition of Abeta. Our study demonstrates that Abeta accumulation affects the balance between VEGF and PEDF in the RPE, and reproduces features characteristic of human AMD, such as RPE atrophy and basal deposit formation in neprilysin gene-disrupted mice.     

Magnetic nanoparticles conjugated with “RPE cell -MCP-1 antibody -VEGF antibody” compounds for the targeted therapy of age-related macular degeneration: a hypothesis

Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly throughout the world. Treatment of AMD utilizing retinal pigment epithelium (RPE) transplantation represents a promising therapy. However, simplex RPE transplantation can only replace the diseased RPE cells, but has no abilities to stop the development of AMD. It has been indicated that oxidization triggers the development of AMD by inducing the dysfunction and degeneration of RPE cells, which results in the upregulation of local monocyte chemotactic protein-1 (MCP-1) expression. MCP-1 induces macrophage recruiment which triggers local inflammation. As a result, the expression of vascular endothelial growth factor (VEGF) is upregulated by MCP-1 mediated inflammation and results in the formation of choroidal neovascularization (CNV). We accordingly propose a targeted therapy of AMD by subretinal transplanting the compound of RPE cell, MCP-1 antibody, and VEGF antibody and using a magnetic system to guide RPE cell compounds conjugated with superparamagnetic iron oxide nanoparticles (SPIONs). Furthermore, SPION-labelled RPE cells can be tracked and detected in vivo by non-invasive magnetic resonance imaging (MRI). This novel RPE cell transplantation methodology seems very promising to provide a new therapeutic approach for the treatment of AMD.     

Neuropilin-1 expression by endothelial cells and retinal pigment epithelial cells in choroidal neovascular membranes

PURPOSE: To determine if vascular endothelial growth factor (VEGF) coreceptor neuropilin-1 (NP-1) is expressed in choroidal neovascularization (CNV) and to localize the expression. DESIGN: Laboratory investigation. METHODS: Six CNV membranes (CNVMs) obtained from patients with subfoveal CNV attributable to age-related macular degeneration (AMD) underwent immunohistochemistry for VEGF receptor-2 (VEGFR-2) and NP-1. The positive cell types were identified by double staining with anticytokeratin, anti-CD31, and antismooth muscle actin (SMA). RESULTS: Immunohistochemical staining revealed positivity for VEGFR-2 and NP-1 in all six CNVMs. Both receptors were strongly expressed by new choroidal endothelial cell forming vessels and CD-31-positive cells in the nonvascular area. They were also expressed in the pigmented retinal pigment epithelial layer and by cytokeratin-positive, nonpigmented retinal pigment epithelium cells in the nonvascular area. The nonpigmented retinal pigment epithelium cells positive for VEGFR-2 and NP-1 were highly colocalized with SMA. CONCLUSIONS: The presence of both VEGF and NP-1 suggest that NP-1 may play a role in the evolution of CNV in AMD.     

Expression of endostatin in human choroidal neovascular membranes secondary to age-related macular degeneration

Endostatin is an endogenous angiogenesis inhibitor which requires E-selectin for its antiangiogenic activity. The aim of this study was to investigate the expression of endostatin in human choroidal neovascular membranes (CNV) secondary to age-related macular degeneration (AMD) with regard to vascularization and proliferative activity. An interventional case series of 36 patients who underwent removal of CNV were retrospectively investigated. Thirty-six CNV were analyzed by light microscopic immunohistochemistry for the expression of CD34 (endothelial cells, EC), CD105 (activated EC), Ki-67 (cell proliferation), Cytokeratin 18 (epithelial cells), VEGF (vascular endothelial growth factor), E-selectin and endostatin. Donor eyes (n=7) including one with AMD were used as controls. Endostatin immunoreactivity was present in choroidal vessels of five as well as in the retinal pigment epithelium (RPE)-Bruch's membrane complex of two donor eyes without AMD. In one eye with AMD, endostatin was detected in RPE, Bruch's membrane and choroidal vessels. Ninety-two percent (33/36) of CNV disclosed endostatin staining. RPE-Bruch's membrane complex, choroidal vessels and stroma were positive in 50% (18/36), 72% (26/36), and 78% (28/36) of the membranes, respectively. Both control eyes and CNV expressed all the investigated markers except E-selectin being positive only in membranes. Endostatin, an endogenous angiogenesis inhibitor, is expressed in CNV and its therapeutic up-regulation may be a new strategy in the treatment of neovascular AMD.     

Surgical treatment of age-related macular degeneration

Choroidal neovascularization (CNV) and geographic atrophy (GA) are serious and potentially devastating complications of age-related macular degeneration (AMD), a leading cause of blindness in the developed world. While anti-vascular endothelial growth factor (VEGF) therapies have emerged as the current standard treatment of choice for choroidal neovascularization, the requirement for indefinite injections places a tremendous burden on physicians and patients, and may have disappointing outcomes in hemorrhagic neovascular AMD. No superior agents exist to treat large subretinal hemorrhage and geographic atrophy. Over the years, several vitreoretinal surgical approaches have been developed to treat macular degeneration, and these surgical options may still play a role in the management of specific complications of AMD. This review summarizes the principles, techniques, and results of surgical treatments for neovascular and non-neovascular age-related macular degeneration, with emphasis on submacular surgery for removal of CNV, full and limited macular translocation, retinal pigment epithelium, and choroid transplants as well as treatment of thick subretinal hemorrhage.     

Pigment epithelium-derived factor is deficient in the vitreous of patients with choroidal neovascularization due to age-related macular degeneration

PURPOSE: Pigment epithelium-derived growth factor (PEDF) is a potent inhibitor of angiogenesis that is found in the normal eye. The purpose of this study is to report decreased levels of PEDF in the vitreous of eyes with choroidal neovascularization (CNV) due to age-related macular degeneration (AMD). DESIGN: Prospective case-control study. METHODS: In a prospective case-control study, undiluted vitreous was collected from nine eyes of nine patients with CNV due to AMD and from an age-matched control group of 12 eyes of 12 patients with retinal disorders not involving neovascularization. Vitreous PEDF and vascular endothelial growth factor (VEGF) concentrations were determined by Western blot analyses and enzyme-linked immunosorbent assay (ELISA), respectively. Angiogenic activities of the vitreous samples were assessed in vitro using an endothelial cell chemotaxis assay. RESULTS: In vitreous samples from nine eyes with CNV due to AMD the mean +/- SD PEDF level was 2.8 ng/microl +/- 1.3 ng/microl. In vitreous samples from 12 age-matched control eyes the mean +/- SD PEDF level was 16.4 ng/microl +/- 7.1 ng/microl. The difference between the two groups was statistically significant (P =.00003). No significant difference in vitreous VEGF concentration was seen between CNV/AMD samples and control samples (P =.23). All CNV/AMD vitreous samples induced endothelial cell migration in vitro. No sample from age-matched non-age-related macular degeneration controls could induce endothelial cell migration, and 11 of 12 were able to block VEGF-induced migration in vitro. This inhibitory activity required active PEDF. CONCLUSION: The vitreous of patients with CNV due to AMD contained lower levels of PEDF and lacked the antiangiogenic activity of vitreous from age-matched controls. This suggests that loss of PEDF creates a permissive environment for CNV patients with AMD.