microRNAs与角膜新生血管

正常角膜的无血管化状态能够维持角膜的免疫赦免和透明性,角膜处于富含血管的环境中却能保持无血管化,归因于内源性血管抑制因子。microRNAs(miRs)是一类内源性小分子非编码RNA,在角膜新生血管形成过程中,多种miRs发挥重要的调控作用,是重要的内源性血管抑制因子。本文就miRs在角膜新生血管中的相关研究进行综述,以期为角膜新生血管的治疗和进一步研究提供借鉴。     

角膜新生血管形成机制

临床上许多角膜病变均能引起角膜新生血管（CNV）,CNV破坏角膜正常微环境,不仅严重影响视力,而且是角膜移植失败的主要原因。近年来,随着对CNV的深入研究,大量实验研究表明许多因素参与CNV的形成过程,本文主要就CNV的形成机制作一综述。     

角膜新生血管的发病机制

角膜新生血管(corneal neovascularization,CNV)形成是角膜化学烧伤、角膜炎等疾病带来的一个难题,严重影响角膜的透明性,最终可导致眼部组织结构的破坏和视功能的损害,是致盲的主要原因之一。随着细胞分子生物学的发展,大量实验研究表明,许多因素参与CNV的形成过程。我们就血管内皮生长因子等主要促角膜血管生长因素及其与CNV的关系作一综述。     

血管生成素与眼部新生血管的关系

血管生成素(angiopoietin,Ang)是特异性作用于血管内皮细胞的生长因子,主要由Ang-1和Ang-2组成;Tie2(tyrosinekinasethatcontainsim-munoglubin-likeloopsandepidermalgrowthfac-tor-similardomains2)是其共同受体。Ang-1促使血管成熟,维持血管稳定。Ang-2则拮抗Ang-1的作用,始动病理性新生血管形成。在眼部新生血管形成过程中Ang/Tie2受体途径起重要作用,抑制Ang/Tie2受体途径可以抑制眼部新生血管形成。     

角膜新生血管的药物治疗进展

角膜在病理因素的作用下产生新生血管。角膜新生血管不但严重影响视力,而且导致角膜移植手术的失败。近年来,国内外对角膜新生血管的治疗取得迅猛发展,但角膜新生血管依然是目前最常见的致盲原因之一。本文综述了近年来角膜新生血管的药物治疗进展。     

角膜新生血管的显影方法

角膜新生血管(corneal neovascularization,CNV)的产生是角膜盲的常见原因,但到目前为止,还没有十分有效的治疗方法。CNV面积这一参数在衡量药物或治疗方案效果好坏时具有重要参考价值。目前有多种方法可对CNV进行显影,包括墨汁灌注、免疫荧光染色等,近年来的光学相干断层成像技术等也是极有潜力的新方法。本文综述了显影CNV的相关方法,希望能对CNV的研究提供参考。     

角膜新生血管的治疗研究进展

近年来,由于免疫学、分子生物学和药理学等学科的进展,对角膜新生血管(corneal neovascularization,CNV)的认识有不少突破,但对CNV的发病机制及其治疗尚有许多问题需待解决。我们主要从药物治疗,基因治疗,激光、手术治疗等方面讨论CNV的治疗进展,从而探讨更为有效的治疗CNV的策略。     

螺内酯对大鼠角膜新生血管生长的影响

目的研究醛固酮受体拮抗剂螺内酯对角膜新生血管(corneal neovasculariza-tion,CNV)生长的影响,探讨其抑制新生血管的机制.方法经缝线诱导CNV模型SD雌性大鼠20只,随机分为CNV对照组、螺内酯灌胃组(灌胃螺内酯150 mg·kg-1～·d-1),每组10只10眼;另取大鼠10只不作任何处理作为正常对照组,比较建模后第3天、第7天、第12天各组新生血管的生长情况并计算CNV生长面积,各组大鼠均于术后第12天取角膜行病理组织学检查,并采用免疫组织化学染色法检测血管内皮生长因子(vascular endothelial growth factor,VEGF)的表达.结果缝线后各时间点上,新生血管对照组CNV的面积分别为(2.549±1.315)mm-2、(13.998±2.999)mm-2、(23.266±2.833)mm-2,螺内酯灌胃组分别为0 mm-2、(8.454±2.830)mm-2、(15.189±3.676)mm-2,2组相比差异具有统计学意义(P<0.05).新生血管对照组角膜组织中VEGF的表达量为22.660±4.158,而螺内酯灌胃组为12.460±1.754,与新生血管对照组相比显著减少,差异具有统计学意义(P<0.05).结论螺内酯全身应用有效地抑制了大鼠CNV的生长,其对VEGF的抑制作用可能是螺内酯抑制CNV的机制之一.     

Subconjunctival bevacizumab for corneal neovascularization

Acta Ophthalmol. 2010: 88: 868–871

Abstract.

Purpose: This work aimed to study and evaluate the effect of subconjunctival bevacizumab injection in patients with corneal neovascularization (CNV) resulting from different ocular surface disorders. Methods: Ten eyes with CNV caused by different ocular surface disorders were studied. All eyes had both major and minor vessel CNV caused by factors such as healed corneal ulcers, long‐standing chronic inflammatory diseases and corneal ischaemia (caused by contact lenses). All eyes received a single subconjunctival injection of 2.5 mg (0.1 ml) bevacizumab. Morphological changes in the major and minor vessels were evaluated using slit‐lamp biomicroscopy and corneal photography. Results: Conspicuous recession of the minor vessels of CNV was observed in all eyes at 2 weeks post‐injection. The extent of CNV of the major vessels was significantly decreased at 2 weeks post‐injection. The level of CNV continued to decrease noticeably for 3 months and then stabilized for the remainder of the 6‐month follow‐up period. Parameters used for evaluation included the total area of CNV, which amounted to 14.0 ± 5.4% of the corneal surface pre‐injection, compared with 9.4 ± 3.9% post‐injection (p < 0.01), reflecting a mean decrease in CNV of 33 ± 8%, and the extent of neovascularization, which decreased from 4.3 ± 1.5 clock hours pre‐injection to 2.4 ± 1.1 clock hours post‐injection (p < 0.01). During the 6‐month follow‐up, none of the 10 eyes showed any complication that could be related to subconjunctival bevacizumab injection. Conclusions: Bevacizumab can be used safely and effectively for CNV resulting from different ocular surface disorders. It represents an effective treatment for minor vessel neovascularization caused by long‐standing chronic inflammation (e.g. trachoma) or long‐standing corneal ischaemia (e.g. contact lenses), as well as for major vessel neovascularization resulting from different causes. Bevacizumab was well tolerated over the 6‐month follow‐up period.     

Inflammatory corneal neovascularization: etiopathogenesis

There is a delicate balance between pro-angiogenic stimuli and anti-angiogenic stimuli in the normal cornea. This balance allows the cornea to normally exist in a relatively avascular state, which is needed for optical clarity and vision. However, in the setting of inflammation, this balance may be shifted in favor of neovascularization. This paper reviews the literature on corneal inflammatory neovascularization beginning with the pro-angiogenic factors, such as Vascular Endothelial Growth Factor and Fibroblast Growth Factor, which help to facilitate the development of new corneal vessels. Subsequently the anti-angiogenic factors and their role in preventing neovascularization in the normal cornea are reviewed. Finally, a review of several etiologies of inflammatory neovascularization is presented with attention to the processes that allow the pro-angiogenic stimuli to overwhelm the anti-angiogenic factors.     

microRNA在角膜新生血管中的研究进展

角膜新生血管（ corneal neovascularization）是影响角膜透明度的主要因素之一,也是同种异体角膜移植术后发生排斥反应的高危因素,因此角膜新生血管形成的调控已成为研究热点。 microRNA是一组内源性非编码小分子RNA,在调控多种生物进程中起重要作用。近年来研究表明, microRNA与角膜新生血管形成有着紧密联系,本文将对目前的研究情况进行综述。     

光动力学治疗角膜新生血管

介绍光动力学治疗（PDT）的机制、光敏剂的种类和PDT用于角膜新生血管的研究现状。PDT应用低能量的光作用于光敏剂，产生对靶组织有毒性的光化学反应。光敏剂易于聚积在肿瘤和新生血管处，被增殖性的细胞摄取，这些组织吸收激光能量，导致自身氧化作用和细胞膜、线粒体、溶酶体和核的直接损伤，最终导致靶组织的新生血管和肿瘤组织的细胞凋亡。临床常用的光敏剂多是卟啉和它的衍生物，包括：苯卟啉衍生物单酸、氯化铝酞花青磺酸盐（CASPc）、SnET2、SINc、菌绿素a等。血啉单醚是一种国产的较理想的单体光动力学治疗新药。国外研究应用ATX-S10和SnET 2等作为光敏剂治疗角膜新生血管，疗效显著。     

Subconjunctival bevacizumab for corneal neovascularization

Objective To report the efficacy of subconjunctival bevacizumab injection in patients with corneal neovascularization (NV). Methods This retrospective interventional case study included two eyes of two patients with corneal NV due to aqueous-deficient dry eye with filamentary keratitis in the first case, and corneal graft failure in the second case. Patients received a subconjunctival injection of 2.5 mg (0.1 ml) bevacizumab. Morphologic changes were investigated by slit-lamp biomicroscopy and corneal photography. Results Corneal NV was dramatically regressed a week after injection in the first case. In the second case, minor vessels were regressed while the major one did not. No infection or inflammation was observed. No relapse was seen within the follow-up of two to three months. Conclusion Subconjunctival injection of bevacizumab may offer an additional strategy for the treatment of corneal NV.     

新生血管的防治靶点及在角膜疾病中的研究现状

新生血管的形成过程中有三个主要的作用靶点(血管内皮细胞、周细胞、细胞外基质)可以调节其生长。每个靶点均有众多的因子参与调节。本文主要以此三个靶点为主线,对新生血管的形成机制及在角膜疾病中的研究现状进行综述。     

Experimental external irradiation of corneal neovascularization

The clinical effect of ionidizing radiation on ocular neovascularizations is controversial not only because of the variety of treatment modalities. The aim of our study was to investigate an experimental model which allows to evaluate radiation parameters and to study the mechanism of the inhibitory effect on neoangiogenesis. METHODS: Corneal angiogenesis was induced by use of a micropocket assay in NZW rabbits. Pellets with 500 ng bFGF in 2% methylecellulose were implanted into the stroma 2.0 mm from the limbus. Initiation of vessel growth occurred on day 3. At this time radiation was performed with different doses (single dose of 15 to 30 Gy or fractionated 5 x 5 Gy) using a 6 MeV linear accelerator. Vascular growth was quantified. RESULTS: Irradiation with a total dose of 25 Gy applied in a fractionated regimen or as single-dose irradiation on the day of surgery or on day 6 after surgery did not significantly reduce neovascular growth. In contrast, postoperative radiation therapy on day 3 was able to reduce the area of ingrowing vessels significantly (P < 0.01). In spite of the relatively high dose there were no significant side effects during the observation period of 8 weeks. CONCLUSION: Our results show that single-dose radiation (> or = 25 Gy) is sufficient to inhibit the growth of corneal neovascularizations. With this model it might be possible to investigate parameters for therapy of ocular neovascularizations as well as the underlying mechanisms.     

重组人内皮抑素滴眼液抑制小鼠角膜新生血管形成的研究

目的　检验重组人内皮抑素对角膜新生血管形成的抑制效果,探索其临床应用价值。 方法　用MTT方法检验重组内皮抑素对血管内皮细胞的增殖抑制活性;用重组人内皮抑素滴眼液,治疗小鼠角膜碱烧伤导致的角膜新生血管形成。 结果　重组人内皮抑素 10μg/mL时可抑制bFGF刺激下HUVEC的增殖,抑制率达到 42 1% (P<0 05); 100μg/mL的内皮抑素可抑制碱烧伤诱导的小鼠角膜新生血管形成,治疗 7d时新生血管长度较未治疗组减少 30 9%(P<0 01),新生血管化面积减少了 13 7% (P<0 01)。 结论　内皮抑素特异地抑制血管内皮细胞增殖,抑制碱烧伤诱导的小鼠角膜新生血管形成,可能成为临床上预防、治疗相关眼科疾患的药物。