Targeting the interleukin-1 receptor for treating ischemic eye diseases

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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.