Plasma Kallikrein and Diabetic Macular Edema
Plasma Kallikrein and Diabetic Macular Edema
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DOI：
10.1007/s11892-010-0127-1
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发表时间：
2010-08-01
影响因子：
4.2
通讯作者：
Feener, Edward P.
中科院分区：
文献类型：
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作者：
Feener, Edward P.
最近的蛋白质组学研究已经在晚期糖尿病视网膜病变患者的玻璃体中发现了钾激肽-激肽系统的组成部分，包括血浆钾激肽-激肽- XII因子和激肽原。在啮齿类动物模型中，激活玻璃体血浆钾激肽可增加视网膜血管通透性；而抑制钾化管激肽系统可减少糖尿病和高血压引起的视网膜渗漏。这些研究结果表明，血浆钾激肽通路的眼内激活可能导致视网膜血管通透性过度，从而导致糖尿病性黄斑水肿。缓激肽激酶系统包含两种独立的、独立调节的丝氨酸蛋白酶，它们产生缓激肽肽：血浆缓激肽激酶和组织缓激肽激酶。组织缓激肽在视网膜和睫状体中表达，通过缓激肽受体在这些组织中共定位，参与发挥自分泌或旁分泌作用。新出现的证据表明血浆钾激肽抑制剂可能提供一个新的治疗机会，以降低视网膜血管通透性。
Recent proteomic studies have identified components of the kallikrein kinin system, including plasma kallikrein, factor XII, and kininogen, in vitreous obtained from individuals with advanced diabetic retinopathy. In rodent models, activation of plasma kallikrein in vitreous increases retinal vascular permeability; whereas inhibition of the kallikrein kinin system reduces retinal leakage induced by diabetes and hypertension. These findings suggest that intraocular activation of the plasma kallikrein pathway may contribute to excessive retinal vascular permeability that can lead to diabetic macular edema. The kallikrein kinin system contains two separate and independently regulated serine proteases that generate bradykinin peptides: plasma kallikrein and tissue kallikrein. Tissue kallikrein is expressed in the retina and ciliary body, where it has been implicated in exerting autocrine or paracrine effects via bradykinin receptors that are colocalized in these tissues. Emerging evidence suggests that plasma kallikrein inhibitors may provide a new therapeutic opportunity to reduce retinal vascular permeability.