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首页> 外文期刊>European Journal of Pharmacology: An International Journal >Pharmacology of novel intraocular pressure-lowering targets that enhance conventional outflow facility: Pitfalls, promises and what lies ahead?
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Pharmacology of novel intraocular pressure-lowering targets that enhance conventional outflow facility: Pitfalls, promises and what lies ahead?

机译：增强常规流出功能的新型眼内降压靶标的药理作用：陷阱，希望以及未来的发展是什么？

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摘要

Intraocular pressure (IOP) lowering drugs that are approved for the treatment of glaucoma and ocular hypertension have limited activity on increasing aqueous humor movement through the trabecular meshwork and Schlemm's canal (TM/SC). The TM/SC complex is considered the conventional outflow pathway and is a primary site of increased resistance to aqueous humor outflow in glaucoma. Novel mechanisms that enhance conventional outflow have shown promise in IOP reduction via modulation of several pathways including Rho kinase, nitric oxide/soluble guanylate cyclase/cGMP, adenosine A(1), prostaglandin EP4/cAMP, and potassium channels. The clinical translatability of these pharmacological modulators based on pre-clinical efficacy models is currently being explored. In addition, identification of pathways from GWAS and other studies involving transgenic rodent models with elevated/reduced IOP phenotypes have begun to yield additional insights into IOP regulation and serve as a source for the next generation of IOP lowering targets. Lastly, improvements in drug delivery technologies to enable sustained IOP reduction are also discussed. (C) 2016 Elsevier B.V. All rights reserved.
机译：被批准用于治疗青光眼和高眼压症的降低眼内压（IOP）的药物在增加通过小梁网和Schlemm管的房水运动方面的活性有限（TM / SC）。 TM / SC复合物被认为是常规的流出途径，并且是对青光眼房水流出阻力增加的主要部位。通过调节多种途径（包括Rho激酶，一氧化氮/可溶性鸟苷酸环化酶/ cGMP，腺苷A（1），前列腺素EP4 / cAMP和钾通道），增强常规流出的新型机制已显示出降低眼压的前景。目前正在探索基于临床前功效模型的这些药理调节剂的临床可翻译性。此外，从GWAS途径鉴定以及其他涉及具有升高/降低的IOP表型的转基因啮齿动物模型的研究已经开始产生对IOP调节的更多见解，并成为下一代降低IOP的靶标。最后，还讨论了改善药物输送技术以实现持续降低眼压的方法。 （C）2016 Elsevier B.V.保留所有权利。

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