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他氟前列素滴眼液的短期和长期角膜血管效应。

Short- and long-term corneal vascular effects of tafluprost eye drops.

机构信息

Department of Ophthalmology, University Hospital of Cologne, Kerpener Strasse 62, 50924 Cologne, Germany.

出版信息

Graefes Arch Clin Exp Ophthalmol. 2013 Aug;251(8):1919-27. doi: 10.1007/s00417-013-2345-0. Epub 2013 Apr 28.

DOI:10.1007/s00417-013-2345-0
PMID:23624591
Abstract

BACKGROUND

Prostaglandin analogs are first line therapy in the treatment of glaucoma, but also display side effects during ocular inflammation. In this context, the potential side effects of prostaglandin analogs on the normally avascular cornea, the main application route for eye drops, are so far not fully defined. Therefore, the aim of this study was to evaluate the vascular effects of the prostaglandin analog tafluprost on the healthy and inflamed cornea.

METHODS

For in vitro studies, blood and lymphatic endothelial cells were treated with tafluprost; cell proliferation was assessed after 48 h. For long-term in vivo studies under healthy conditions, naïve corneas of BALB/c mice were treated with tafluprost eye drops for 4 weeks. For short-term in vivo studies under inflammatory conditions, corneal inflammation was induced by suture placement; mice then received tafluprost eye drops for 1 week. Afterwards, corneas were stained with CD31 as panendothelial and LYVE-1 as lymphendothelial (and macrophage) marker.

RESULTS

In vitro, tafluprost did not alter blood or lymphatic endothelial cell proliferation. In vivo, there was no change in limbal blood or lymphatic vessel anatomy after long-term treatment with tafluprost. Short-term treatment with tafluprost under inflammatory conditions did not influence the recruitment of LYVE-1 positive macrophages into the cornea. Moreover, treatment of inflamed corneas with tafluprost did not significantly influence corneal hem- and lymphangiogenesis.

CONCLUSIONS

Tafluprost does not affect blood and lymphatic vessel growth, neither under resting nor under inflammatory conditions. These findings suggest a safe vascular profile of tafluprost eye drops at the inflammatory neovascularized cornea.

摘要

背景

前列腺素类似物是治疗青光眼的一线药物,但在眼部炎症期间也会显示出副作用。在这种情况下,前列腺素类似物在正常无血管角膜(眼药水的主要应用途径)上的潜在副作用迄今为止尚未完全确定。因此,本研究的目的是评估前列腺素类似物他氟前列素对健康和炎症角膜的血管作用。

方法

在体外研究中,用他氟前列素处理血液和淋巴管内皮细胞;48 小时后评估细胞增殖。在健康条件下进行长期体内研究,用他氟前列素眼药水处理 naive BALB/c 小鼠角膜 4 周。在炎症条件下进行短期体内研究,通过缝线放置诱导角膜炎症;然后用他氟前列素眼药水治疗 1 周。之后,用 CD31 作为全内皮和 LYVE-1 作为淋巴管内皮(和巨噬细胞)标志物对角膜进行染色。

结果

在体外,他氟前列素没有改变血液或淋巴管内皮细胞的增殖。在体内,长期用他氟前列素治疗后,角膜缘血液或淋巴管解剖结构没有变化。在炎症条件下短期用他氟前列素治疗不会影响 LYVE-1 阳性巨噬细胞招募到角膜。此外,用他氟前列素治疗炎症性角膜不会显著影响角膜血管生成和淋巴管生成。

结论

他氟前列素既不会影响静止状态下也不会影响炎症状态下的血管生长。这些发现表明,他氟前列素眼药水在炎症性新生血管化角膜上具有安全的血管特征。

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本文引用的文献

1
Tafluprost once daily for treatment of elevated intraocular pressure in patients with open-angle glaucoma.他氟前列素每日一次用于治疗开角型青光眼患者的眼压升高。
Clin Ophthalmol. 2013;7:7-14. doi: 10.2147/OPTH.S30951. Epub 2012 Dec 21.
2
Increased prostaglandin E2 (PGE2) levels in proliferative diabetic retinopathy, and correlation with VEGF and inflammatory cytokines.增殖性糖尿病视网膜病变中前列腺素 E2(PGE2)水平升高,与 VEGF 和炎症细胞因子相关。
Invest Ophthalmol Vis Sci. 2012 Aug 27;53(9):5906-11. doi: 10.1167/iovs.12-10410.
3
Change in prostaglandin expression levels and synthesizing activities in dry eye disease.
他氟前列素(一种最近开发的抗青光眼前列腺素类似物)的眼表细胞毒性及安全性评估
Ophthalmol Eye Dis. 2014 Feb 13;6:5-12. doi: 10.4137/OED.S12445. eCollection 2014.
干眼症中前列腺素表达水平和合成活性的变化。
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The use of prostaglandin analogs in the uveitic patient.前列腺素类似物在葡萄膜炎患者中的应用。
Semin Ophthalmol. 2011 Jul-Sep;26(4-5):285-9. doi: 10.3109/08820538.2011.588650.
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Blockade of insulin receptor substrate-1 inhibits corneal lymphangiogenesis.阻断胰岛素受体底物-1 抑制角膜淋巴管生成。
Invest Ophthalmol Vis Sci. 2011 Jul 29;52(8):5778-85. doi: 10.1167/iovs.10-6816.
6
Suppression of inflammatory corneal lymphangiogenesis by application of topical corticosteroids.局部应用皮质类固醇抑制炎性角膜淋巴管生成。
Arch Ophthalmol. 2011 Apr;129(4):445-52. doi: 10.1001/archophthalmol.2011.42.
7
Genetic heterogeneity of lymphangiogenesis in different mouse strains.不同小鼠品系淋巴管生成的遗传异质性。
Am J Pathol. 2010 Jul;177(1):501-10. doi: 10.2353/ajpath.2010.090794. Epub 2010 May 20.
8
Cutting edge: lymphatic vessels, not blood vessels, primarily mediate immune rejections after transplantation.前沿:淋巴管而非血管,在移植后主要介导免疫排斥。
J Immunol. 2010 Jan 15;184(2):535-9. doi: 10.4049/jimmunol.0903180. Epub 2009 Dec 16.
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Topical beta blockers in asthmatic patients-is it safe?哮喘患者外用β受体阻滞剂——安全吗?
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Side effects associated with prostaglandin analog therapy.与前列腺素类似物疗法相关的副作用。
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