微小RNAs在眼组织的表达及其与眼科疾病的关系

微小核糖核酸（miRNAs）是内源性小分子非编码调控RNAs,通过抑制转录或降解mRNA调控基因的表达。研究发现miRNAs涉及组织分化和生长等许多重要的生物进程,显示出组织特异性和生长阶段特异性,也参与新生血管形成及很多病理进程,如肿瘤血管新生、氧化应激、免疫反应和炎症。目前,视网膜、晶状体和角膜的miRNAs转录组已经建立,并可能在未来作为眼科疾病治疗的手段之一。就miRNAs在眼组织中的分布及其在眼病中的异常表达进行综述。     

炎性细胞因子与新生血管性眼病

新生血管性眼病是引起人类不可逆视力损害的主要病因.尽管眼内抗血管内皮生长因子药物治疗已成为临床中新生血管性眼病的重要疗法之一,但该疗法本身疗效不稳定且存在诸多的潜在风险和并发症.因此探寻更明确有效的治疗靶点是必要的.研究表明,肿瘤坏死因子-α、白细胞介素-1、白细胞介素-6和白细胞介素-18等炎性细胞因子与新生血管性眼病关系密切,本文就近些年来与新生血管性眼病相关的炎性细胞因子作一综述.     

哺乳动物视网膜microRNA的表达及功能

microRNAs(miRNAs)是一类长约22个核苷酸的内源性非编码单链RNA,在维系几乎所有组织或器官系统的正常发育和生理功能等方面都起着非常重要的作用,主要通过降解靶基因mRNAs或抑制靶基因mRNAs的翻译,从而沉默特定靶基因发挥作用.据预测人类超过1/3的蛋白编码基因受miRNAs的调控.越来越多的研究表明很多miRNAs在眼部组织中有特异性的表达,其中至少有78个miRNAs在视网膜组织中表达.本文主要就miRNAs在哺乳动物视网膜中的表达及其相关功能的最新研究进展作一综述.     

VEGF与眼内血管新生

眼内新生血管是很多眼病致盲的重要原因,例如糖尿病视网膜病变、年龄相关性黄斑变性、早产儿视网膜病变、视网膜中央或分支静脉阻塞、角膜炎和眼外伤等.生长因子中的血管内皮生长因子(vascular endothelial growth factor,VEGF)家族是眼内血管新生的关键因素.在一些眼病中,它通过调控病理性血管发生和增加血管通透性而起作用.本文我们主要阐述眼内新生血管的形成机制和治疗方面的新进展,对VEGF 家族的结构、理化特性、VEGF及受体在眼内血管新生中的作用以及针对血管新生的防治措施进行综述.     

微小RNA在糖尿病视网膜病变新生血管生成中的研究进展

微小RNA(miRNA)是一类内生的、长度约20 ～ 24个核苷酸的具有组织特异性和高度保守的RNA,通过与mRNA互补配对在转录后水平降解mRNA或抑制mRNA翻译来负调控靶基因的表达.多项研究已表明miRNA的亚型基因miR-126、miR-31、miR-200b和miR-29等在一定程度上与糖尿病视网膜病变(DR)的新生血管生成有关,通过一系列调控血管内皮生长因子(VEGF)的表达,进而抑制或促进血管新生,而VEGF是一种新生血管的主要促进因子,能够特异性的刺激血管内皮细胞的增生及新生血管生成,破坏血-视网膜屏障,加快DR的进展.因此,揭示miRNA在DR新生血管形成中的作用及其机制是未来DR机制研究的重要方向,并可为DR的防治提供新的策略.现就miRNA在DR新生血管形成的研究进展作一综述.     

周细胞在新生血管性眼病中的作用研究进展

新生血管性眼病以病理性新生血管形成为病理特征,是威胁眼健康的主要疾病。近年来,各种新生血管性眼病发病率逐年提高,已成为严重的公共卫生问题,引起了广泛关注。病理性新生血管是多种细胞成分、多种病理因素互相包含、交互影响下形成的,单独干预其中一种因素往往很难达到理想治疗效果,因此需要更深入地研究新生血管的病理过程,探究新的调控新生血管的因子,以发现更有效的治疗方法。近年来研究发现,周细胞在多种新生血管性眼病的发生发展中起重要作用,针对周细胞采取干预措施将影响这些疾病的病理过程。本文将对新生血管性眼病中周细胞的具体作用以及调控周细胞的因素作出综述,为新生血管性眼病的治疗提供新的思路和方向。     

血管内皮生长因子与眼内新生血管

眼内新生血管是多种致盲眼病的病理生理基础,新生血管形成受多种因子调控,其中血管内皮生长因子(VEGF)是最重要的细胞因子。它与特异性受体结合后通过复杂机制促进血管内皮细胞增殖、迁移和通透性增加。缺氧可诱导VEGF表达,VEGF通过NO的介导作用发挥促血管新生的作用。还有多种抑制和促进血管因子共同作用于血管内皮细胞。目前,人们通过基因手段抑制VEGF及其受体达到抑制血管新生的作用,为眼内新生血管性疾病开辟前景。     

视网膜新生血管生物药物治疗研究进展

眼内新生血管的发生是许多眼病的病理基础和重要临床表现,而血管内皮生长因子(VEGF)是刺激不正常的血管生长以及造成血管壁渗漏的主因,因此抗VEGF靶分子治疗成为当今的研究热点.本文综述了近年来视网膜新生血管生物药物治疗新进展,包括VEGF反义寡聚脱氧核苷酸、VEGF抗体、RNA干扰类药物等.这些方法均显示出令人振奋的效果,但仍需要经过长期、系统的临床试验检验其安全性、有效性.     

新生血管性眼病基因治疗的研究进展

随着对多种分子信号与新生血管关系的深入研究,发现促血管生成因子与抑制因子之间的失衡是新生血管生成的重要原因.基因治疗是指将基因导入人体细胞使其发挥生物学效应,从而治疗疾病的一种技术方法.应用基因转染技术将外源基因导入眼内,通过下调促血管生成因子的表达或上调抑制因子的表达,重塑其间的平衡,将为新生血管性眼病的防治提供新的思路.     

微小RNA在糖尿病视网膜病变发病机制中的作用

微小RNA（micoRNA）是一类高度保守、非编码的小分子RNA,通过与mRNA互补配对在转录后水平降解mRNA或抑制mRNA翻译来负调控靶基因的表达,并可能调控着几乎每一个细胞生理进程.研究发现微小RNA的异常表达谱对于糖尿病视网膜病变（diabetic retinopathy,DR）的发病机制有着至关重要的作用.微小RNA在不同的刺激因素下通过靶向调控核因子-κB、缺氧诱导因子-1/血管内皮生长因子、p53等与DR发生发展密切相关的靶基因,产生不同的细胞生物学效应,从而广泛调节视网膜各类细胞在炎症发生、新生血管形成、增生和凋亡等方面的病理过程.异常表达的微小RNA及其功能靶标的发现不仅丰富了对DR发病机制的阐述,也为DR的早期预防和探索基因靶向治疗提供新的突破点.     

眼部新生血管与抗血管内皮生长因子治疗

眼部新生血管性病变是致盲的主要原因之一,可见于多种眼底疾病,其确切的发病机制尚不完全清楚.大量的研究证据表明血管内皮生长因子(VEGF)是新生血管形成的关键调控因子.本文对VEGF的特性、VEGF在眼部新生血管形成中的作用和抗VEGF治疗进行综述.     

信号转导和转录激活因子3与眼部新生血管

眼部新生血管与多种眼部疾病相关,是视力损伤的主要原因之一。众多信号通路和复杂调控机制的参与,使得眼部新生血管的治疗相对棘手。信号转导与转录激活因子3（STAT3）是近年来研究较多的一种转录因子,参与细胞多种生物功能的改变,并调控体内新生血管的生成过程。目前STAT3在眼部新生血管发生中的重要作用已受到关注,为眼部新生血管的防治提供新的思路。就STAT3与眼部新生血管之间的相关性研究进行综述。     

骨桥蛋白与眼部新生血管性疾病研究进展

眼部新生血管是眼部疾病中致盲的主要原因之一.常见的致盲眼病,如糖尿病视网膜病变、年龄相关性黄斑变性、感染性角膜炎等均与新生血管存在一定的关系.骨桥蛋白（OPN）是一种能够促进血管再生与组织修复的糖蛋白,在角膜、脉络膜和视网膜新生血管中表达增多,能够促进新生血管的发生.OPN与新生血管的关系为新生血管性疾病的研究和治疗提供了新的方向.从OPN促进角膜新生血管、脉络膜新生血管、视网膜新生血管生成3个方面对OPN与眼部新生血管性疾病的关系研究进展进行综述.     

内皮抑素在抗新生血管性眼病治疗中的研究进展

眼部新生血管性疾病严重危害视力,目前的动物实验已证明内皮抑素(endostatin,ES)有望成为一种新型、有效的抑制眼部新生血管的药物。我们就ES在抗新生血管性眼病治疗中的研究进展作一综述。     

Presumed ocular histoplasmosis syndrome: update on epidemiology, pathogenesis, and photodynamic, antiangiogenic, and surgical therapies.

Presumed ocular histoplasmosis involves the classic triad of discrete atrophic choroidal scars in the macula or midperiphery known as histo spots, peripapillary atrophy, and choroidal neovascularization, which leads to severe loss of central vision. The histo spots from which the choroidal neovascularization develop do not show active inflammation but do represent focal defects in Bruch membrane that could facilitate development of choroidal neovascularization. The macular photocoagulation studies unequivocally show the benefit of photocoagulation compared with observation in reducing the risk of vision loss in patients with presumed ocular histoplasmosis, well defined extrafoveal or juxtafoveal choroidal neovascularization, and choroidal neovascularization in the peripapillary area. However, laser treatment itself causes an absolute scotoma correlating with the site of the laser photocoagulation scar, and subfoveal choroidal neovascularization is not amenable to laser photocoagulation because this would cause a blinding central scotoma. Consequently, other treatments have been sought. The Verteporfin in Ocular Histoplasmosis study evaluated photodynamic therapy for subfoveal choroidal neovascularization caused by presumed ocular histoplasmosis and demonstrated stabilization of the choroidal neovascularization and visual acuity benefit. In addition to photodynamic therapy, antiangiogenic compounds are being developed for choroidal neovascularization caused by age-related macular degeneration, and these agents will likely be of benefit in presumed ocular histoplasmosis associated choroidal neovascularization. Finally, submacular surgery for the removal of subfoveal choroidal neovascularization has promising results. The results of these research efforts will produce more effective therapeutic approaches in the future.     

Intravitreal bevacizumab (Avastin) as primary and rescue treatment for choroidal neovascularization secondary to ocular toxoplasmosis

BACKGROUND: Treatment modalities for choroidal neovascularization due to ocular toxoplasmosis include laser photocoagulation, surgery, corticosteroids, and verteporfin therapy. Intravitreal injection of bevacizumab in the treatment of choroidal neovascularization due to other conditions appears to be an effective and safe therapeutic option. CASE REPORTS: We report two young patients with choroidal neovascularization secondary to ocular toxoplasmosis who received a single intravitreal injection of bevacizumab as primary or rescue therapy. After a follow-up of 12 and 10 months, respectively, visual acuity improved, and features of active neovascularization resolved with no recurrence. No adverse events were recorded. CONCLUSION: Intravitreal injection of bevacizumab appears to be an effective and safe treatment modality in patients with choroidal neovascularization secondary to ocular toxoplasmosis. Further evaluation with a longer follow-up period is needed to confirm these findings.     

Topical bevacizumab and ocular surface neovascularization in patients with stevens-johnson syndrome

PURPOSE: To evaluate the efficacy and safety of topical bevacizumab on ocular surface neovascularization among patients with Stevens-Johnson syndrome. METHODS: This was a retrospective, interventional case report. Three eyes of 2 patients were examined. Bevacizumab (25 mg/mL) eyedrops were applied 4 times daily for a period of 3 months. Main outcome measures were improvement of symptoms, visual acuity, degree of ocular surface neovascularization, corneal opacification, conjunctival injection, and occurrence of adverse events. RESULTS: Both patients completed the 3-month observation period and reported that it significantly improved ocular comfort. At the end of the study period, visual acuity improved in all 3 eyes; all eyes were observed to have decreased ocular surface neovascularization, corneal opacification, and conjunctival injection. No serious adverse events were reported. CONCLUSIONS: Topical bevacizumab is well tolerated and may be effective in improving comfort and inducing regression of ocular surface neovascularization, conjunctival injection, and corneal opacification in patients with ocular surface disease caused by Stevens-Johnson syndrome. Further controlled and long-term studies are needed to fully evaluate the long-term effects of this novel treatment.     

Regression of ocular neovascularization in response to increased expression of pigment epithelium-derived factor

PURPOSE: Several pharmacologic treatments have been shown to reduce ocular neovascularization when administered before the onset of angiogenic stimuli, but none have been shown to cause regression of already established ocular neovascularization. In this study, the authors tested the effect of adenoviral vectored pigment epithelium-derived factor (PEDF) gene transfer on established neovascularization in transgenic mice with expression of vascular endothelial growth factor (VEGF) in photoreceptors (rho/VEGF mice) and in a model of choroidal neovascularization. METHODS: Two weeks after the onset of VEGF transgene expression in rho/VEGF mice or 2 weeks after laser-induced rupture of Bruch's membrane in wild-type mice, subgroups of mice were killed, and the baseline amount of neovascularization was measured by image analysis. The remainder of the mice received an intravitreous or subretinal injection of adenoviral vector containing a PEDF expression construct (AdPEDF.11) or control vector (AdNull.11). RESULTS: Seven days after injection in rho/VEGF mice or 10 days after injection in the choroidal neovascularization model, the amount of neovascularization in AdPEDF.11-injected eyes was significantly less than the baseline level, indicating that regression of neovascularization had occurred. There was TUNEL staining within choroidal neovascular lesions in eyes injected with AdPEDF.11. Eyes given a subretinal injection of AdNull.11 had TUNEL-positive cells in the retina, but none within areas of choroidal neovascularization. CONCLUSIONS: These data indicate that increased expression of PEDF causes regression of ocular neovascularization by promoting apoptosis of cells within neovascular lesions and possibly represents a new treatment paradigm for patients with established ocular neovascularization.