Targeting the interleukin-1 receptor for treating ischemic eye diseases

缺血性视网膜病是由损害视网膜的血管阻塞引起的疾病。视网膜是眼睛的一部分，拥有感知光线的细胞，以及为这些细胞提供营养的血管。氧化应激和炎症是缺血性视网膜病的早期共同特征，例如与早产和糖尿病相关的那些，这两种最常见的视网膜病分别发生在儿童和65岁以下的成人中。炎症加剧这些血管中的异常，导致血管内液体渗漏和毛细血管闭塞，从而引起视网膜退化，导致视力丧失。这些疾病目前还没有治愈的方法。治疗通常旨在使用激光光凝破坏异常血管。尝试使用类固醇和抑制血管生长的药物（所谓的抗VEGF治疗）已经显示出有限的成功，部分原因是它们要么发挥适度的抗炎作用，要么只能解决晚期水肿和视网膜前新生血管形成，而不能解决诱发炎症。该研究通过使用新型化合物靶向白细胞介素-1受体（IL-1 R）来解决缺血性视网膜病变的炎症方面，该化合物干扰炎症过程，防止血管破坏并导致血管密度正常化，而不影响局部免疫监视和细胞保护。我们对新IL-1 R调节剂的初步研究结果值得进一步研究，以增强其作为治疗这些主要视力障碍疾病的新疗法的潜力。

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.