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Renu A. Kowluru, Sarah Odenbach; Role of Interleukin-1β in the Development of Retinopathy in Rats: Effect of Antioxidants. Invest. Ophthalmol. Vis. Sci. 2004;45(11):4161-4166. doi: 10.1167/iovs.04-0633.
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purpose. Diabetic retinopathy is shown to share many similarities with chronic inflammatory disease, and in diabetes, accelerated apoptosis of retinal capillary cells is evident before histopathology can be seen. The purpose of this study was to examine the effect of interleukin (IL)-1β on capillary cell apoptosis in rat retina and to determine the effect of antioxidants on diabetes-induced changes in retinal IL-1β.
methods. The effect of injection of IL-1β into the vitreous (5 ng/5 μL) of normal rats on capillary cell apoptosis (detected by terminal transferase dUTP nick-end labeling [TUNEL]) and formation of acellular capillaries was investigated in the trypsin digested retinal microvessels. The levels of IL-1β were quantified (by ELISA and Western blot) in the retina of rats diabetic for 2 months, and the effect of administration of antioxidants on diabetes-induced changes in retinal IL-1β was determined.
results. The number of TUNEL-positive capillary cells in the retinal microvessels obtained from normal rats that received intravitreal injection of IL-1β was increased by more than threefold and that of acellular capillaries by more than twofold, compared with the microvessels obtained from rats that received an intravitreal injection of PBS (5 μL) or BSA (5 ng/5 μL). IL-1β also increased the levels of 8-hydroxy-2′-deoxyguanosine (an indicator of oxidative stress) and nitric oxide by more than 40% and activated NF-κB by 35% to 55%. Two months of diabetes in rats increased retinal IL-1β levels by more than twofold, and antioxidants inhibited such increases.
conclusions. IL-1β, by activation of NF-κB and an increase in oxidative stress, plays an important role in the retinal microvascular disease that is characteristic of diabetic retinopathy. Antioxidants inhibit diabetes-induced increases in retinal IL-1β. These studies offer a possible rationale to test IL-1β-targeted therapies to inhibit the development of retinopathy in diabetes.
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