β肾上腺素能受体拮抗剂治疗眼部新生血管疾病的研究进展

Research progress ofβ-adrenergic receptor antagonists in the treatment of ocular neovascular diseases

眼部新生血管形成是糖尿病视网膜病变、早产儿视网膜病变、视网膜中央静脉阻塞和老年性黄斑变性等多种眼部疾病的病理学改变,严重影响患者视力。β受体在结膜、角膜上皮细胞、角膜内皮细胞、眼外肌、小梁网、睫状肌、晶状体和视网膜中均有表达。β肾上腺素能受体拮抗剂与β受体结合,通过抑制血管内皮生长因子(VEGF)、缺氧诱导因子-1、白细胞介素-6等促血管生成细胞因子,降低巨噬细胞相关炎症反应,增加抗血管生成因子表达来发挥抗血管生成作用。其在治疗角膜新生血管、脉络膜新生血管、早产儿视网膜病变时,可显著减少新生血管面积,延缓疾病进展,联合应用抗VEGF药物可减少抗VEGF药物的给药频率。在有效的治疗浓度下,β肾上腺素能受体拮抗剂表现出良好的耐受性;且其较抗VEGF药物有更广泛的靶点,为角膜、脉络膜和视网膜新生血管等眼部新生血管性疾病提供了新的治疗策略。

Ocular neovascularization is a pathological change in various ocular diseases such as diabetic retinopathy,retinopathy of prematurity,central retinal vein occlusion and age-related macular degeneration,which seriously affects patient's vision.βreceptors are expressed in conjunctiva,corneal epithelial cells,corneal endothelial cells,extraocular muscles,trabecular meshwork,ciliary muscle,lens and retina.βadrenergic receptor antagonists bind toβreceptors to exert anti-angiogenic effects by inhibiting the expression of vascular endothelial growth factor(VEGF),hypoxia-inducible factor-1,interleukin-6 and other angiogenic cytokines;reducing macrophage-related inflammatory response;increasing the expression of anti-angiogenic factors.In the treatment of corneal neovascularization,choroidal neovascularization,and retinopathy of prematurity,it can significantly reduce the area of neovascularization and delay disease progression.Co-administration of anti-VEGF drugs can reduce the frequency of administration of anti-VEGF drugs.At effective therapeutic concentrations,β-adrenergic receptor antagonists are well tolerated;they have broader targets than anti-VEGF drugs,which offers new treatment strategies for ocular neovascularization such as corneal,choroidal and retinal neovascularization.