The β-adrenergic system as a possible new target for pharmacologic treatment of neovascular retinal diseases
The β-adrenergic system as a possible new target for pharmacologic treatment of neovascular retinal diseases
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DOI：
10.1016/j.preteyeres.2014.06.001
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发表时间：
2014-09-01
影响因子：
17.8
通讯作者：
Bagnoli, Paola
中科院分区：
文献类型：
--
作者：
Casini, Giovanni;Dal Monte, Massimo;Bagnoli, Paola
视网膜新生血管病变，如糖尿病性视网膜病变、早产儿视网膜病变（ROP）和年龄相关性黄斑变性，可以通过玻璃体内注射靶向血管内皮生长因子（VEGF）（新生血管生成的主要诱导物）的药物进行治疗;然而，需要进一步改进和替代策略。在过去的几年里，一个激烈的研究活动集中在β-肾上腺素能系统。结果表明，在不同的实验模型中，β-肾上腺素能功能的降低可能会导致血管变化的减少或加剧，从而表明β-肾上腺素受体（β-AR）调节可能具有双重作用，这取决于实验设置。在增殖性视网膜病的体内模型中，大多数数据表明通过阻断特异性β-AR对血管变化具有强烈的抑制作用。特别是，β 2-AR似乎主要参与这些反应，β 1-/β 2-AR阻断剂普萘洛尔在抑制由缺氧损伤引起的VEGF表达增加和随后的新生血管反应方面非常有效。这些观察结果促使在患有ROP的早产儿中进行临床试验，其中口服普萘洛尔在疗效方面产生了积极的结果，尽管也报告了安全性问题。此外，以滴眼液形式使用普萘洛尔局部给药的可能性开辟了人类给药的新的潜在途径。应该考虑的另一点是，有数据表明β-AR具有显著的抗凋亡作用，因此，如果使用β-AR阻滞剂抑制异常新生血管形成，可能会造成神经元活力受损的负担。(C)2014由Elsevier Ltd.出版
Retinal neovascular pathologies, such as diabetic retinopathy, retinopathy of prematurity (ROP) and agerelated macular degeneration, may be treated with intravitreal injections of drugs targeting vascular endothelial growth factor (VEGF), the main inducer of neoangiogenesis; however further improvements and alternative strategies are needed. In the last few years, an intense research activity has focused on the beta-adrenergic system. The results indicate that, in different experimental models, a decrease of the beta-adrenergic function may result either in reduction or in exacerbation of the vascular changes, thus suggesting possible dual effects of beta-adrenoreceptor (beta-AR) modulation depending on the experimental setting. In in vivo models of proliferative retinopathies, most of the data point to a strong inhibitory role against vascular changes exerted by the blockade of specific beta-ARs. In particular, the beta 2-AR seems to be the mostly involved in these responses, and the beta 1-/beta 2-AR blocker propranolol results highly effective in inhibiting both the increase of VEGF expression caused by a hypoxic insult and the consequent neovascular response. These observations have prompted clinical trials in preterm infants with ROP, where oral administrations of propranolol produced positive results in terms of efficacy, although safety problems were also reported. In addition, the possibility of using topical propranolol administrations in the form of eye drops opens new potential routes of drug administration in humans. A further point that should be considered is that there are data demonstrating significant antiapoptotic effects exerted by beta-ARs, therefore if beta-AR blockers were used to inhibit aberrant neovascularization, there may be a burden to pay in terms of impaired neuronal viability. (C) 2014 Published by Elsevier Ltd.