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基于发病机制的年龄相关性黄斑变性的药物治疗

[Pharmacological therapy of age-related macular degeneration based on etiopathogenesis].

作者信息

Fischer Tamás

出版信息

Orv Hetil. 2015 Nov 15;156(46):1847-58. doi: 10.1556/650.2015.30207.

Abstract

It is of great therapeutic significance that disordered function of the vascular endothelium which supply the affected ocular structures plays a major role in the pathogenesis and development of age-related macular degeneration. Chronic inflammation is closely linked to diseases associated with endothelial dysfunction, and age-related macular degeneration is accompanied by a general inflammatory response. According to current concept, age-related macular degeneration is a local manifestation of systemic vascular disease. This recognition could have therapeutic implications because restoration of endothelial dysfunction can restabilize the condition of chronic vascular disease including age-related macular degeneration as well. Restoration of endothelial dysfunction by pharmaacological or non pharmacological interventions may prevent the development or improve endothelial dysfunction, which result in prevention or improvement of age related macular degeneration as well. Medicines including inhibitors of the renin-angiotensin system (converting enzyme inhibitors, angiotensin-receptor blockers and renin inhibitors), statins, acetylsalicylic acid, trimetazidin, third generation beta-blockers, peroxisome proliferator-activated receptor gamma agonists, folate, vitamin D, melatonin, advanced glycation end-product crosslink breaker alagebrium, endothelin-receptor antagonist bosentan, coenzyme Q10; "causal" antioxidant vitamins, N-acetyl-cysteine, resveratrol, L-arginine, serotonin receptor agonists, tumor necrosis factor-alpha blockers, specific inhibitor of the complement alternative pathway, curcumin and doxycyclin all have beneficial effects on endothelial dysfunction. Restoration of endothelial dysfunction can restabilize chronic vascular disease including age-related macular degeneration as well. Considering that the human vascular system is consubstantial, medicines listed above should be given to patients (1) who have no macular degeneration but have risk factors for the disease and are older than 50 years; (2) who have been diagnosed with unilateral age-related macular degeneration in order to prevent damage of the contralateral eye; (3) who have bilateral age-related macular degeneration in order to avert deterioration and in the hope of a potential improvement. However, randomised prospective clinical trials are still needed to elucidate the potential role of these drug treatments in the prevention and treatment of age-related macular degeneration.

摘要

供应受影响眼部结构的血管内皮功能紊乱在年龄相关性黄斑变性的发病机制和发展中起主要作用,这具有重大的治疗意义。慢性炎症与内皮功能障碍相关疾病密切相关,年龄相关性黄斑变性伴有全身性炎症反应。根据当前概念,年龄相关性黄斑变性是系统性血管疾病的局部表现。这一认识可能具有治疗意义,因为内皮功能障碍的恢复可以使包括年龄相关性黄斑变性在内的慢性血管疾病状况重新稳定。通过药物或非药物干预恢复内皮功能障碍可能预防其发展或改善内皮功能障碍,这也会导致预防或改善年龄相关性黄斑变性。包括肾素 - 血管紧张素系统抑制剂(转化酶抑制剂、血管紧张素受体阻滞剂和肾素抑制剂)、他汀类药物、乙酰水杨酸、曲美他嗪、第三代β受体阻滞剂、过氧化物酶体增殖物激活受体γ激动剂、叶酸、维生素D、褪黑素、晚期糖基化终产物交联破坏剂阿格列净、内皮素受体拮抗剂波生坦、辅酶Q10;“因果性”抗氧化维生素、N - 乙酰半胱氨酸、白藜芦醇、L - 精氨酸、5 - 羟色胺受体激动剂、肿瘤坏死因子 - α阻滞剂、补体替代途径特异性抑制剂、姜黄素和强力霉素在内的药物均对内皮功能障碍有有益作用。内皮功能障碍的恢复也可以使包括年龄相关性黄斑变性在内的慢性血管疾病重新稳定。考虑到人类血管系统是同质的,上述药物应给予以下患者:(1)没有黄斑变性但有该疾病危险因素且年龄超过50岁的患者;(2)已被诊断为单侧年龄相关性黄斑变性以预防对侧眼受损的患者;(3)患有双侧年龄相关性黄斑变性以避免病情恶化并希望有可能改善的患者。然而,仍需要随机前瞻性临床试验来阐明这些药物治疗在年龄相关性黄斑变性预防和治疗中的潜在作用。

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