Targeting the interleukin-1 receptor for treating ischemic eye diseases

靶向白介素 1 受体治疗缺血性眼病

• 批准号: 493638-2016
• 负责人: Lubell, William
• 金额: $ 18.59万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Collaborative Health Research Projects
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=621870
• 关键词: Targeting; interleukin; receptor; treating; ischemic

Ischemic retinopathies are diseases caused by obstruction of blood vessels that damage the retina. The retina is the part ofthe eye that possesses cells which sense light, as well as blood vessels that bring nutrients to these cells. Oxidant stressand inflammation are early intertwined common features of ischemic retinopathies, such as those associated withprematurity and diabetes, the two most common retinopathies, respectively of childhood and adults under the age of 65.Inflammation elicits abnormalities in these vessels causing leakage of intravascular fluids and obliteration of capillaries thatcause deterioration of the retina resulting in vision loss. No cures exist presently for these diseases. Treatments typicallyaim to destroy abnormal blood vessels using laser photocoagulation. Attempts to use steroids and agents that arrest bloodvessel growth (so called anti-VEGF therapy) have shown limited success, in part because they either exert modest antiinflammatoryeffects or only tackle the late stage edema and pre-retinal neovascularization, without addressing thepredisposing inflammation. The proposed research tackles the inflammatory aspect of ischemic retinopathy by targeting theinterleukin-1 receptor (IL-1R) using novel compounds that interfere with the inflammatory process, prevent vessel destructionand lead to normalization of vessel density, without compromising local immune surveillance and cytoprotection. Ourpromising preliminary results with new IL-1R modulators merits further study to enhance their potential as novel therapeuticsto treat these major vision-robbing diseases.

缺血性视网膜病变是由于血管阻塞损害视网膜而引起的疾病。视网膜是眼睛的一部分，它拥有感知光线的细胞，以及为这些细胞带来营养的血管。氧化应激和炎症是缺血性视网膜病变的早期相互交织的共同特征，例如与早熟和糖尿病有关的视网膜病变，这两种最常见的视网膜病变分别发生在儿童和65岁以下的成年人。炎症引起这些血管的异常，导致血管内液体泄漏和毛细血管闭塞，导致视网膜恶化，导致视力丧失。目前还没有治愈这些疾病的方法。治疗的典型目的是用激光光凝摧毁异常血管。使用类固醇和抑制血管生长的药物(所谓的抗血管内皮生长因子疗法)的尝试显示出有限的成功，部分原因是它们要么起到适度的抗炎作用，要么只治疗晚期浮肿和视网膜前新生血管，而没有治疗易患炎症。这项拟议的研究通过靶向白细胞介素1受体(IL-1R)来治疗缺血性视网膜病变的炎症方面，使用新的化合物干扰炎症过程，防止血管破坏，导致血管密度正常化，而不影响局部免疫监测和细胞保护。我们对新的IL-1R调节剂有希望的初步结果值得进一步研究，以增强其作为治疗这些主要的视觉剥夺疾病的新疗法的潜力。