Beneficial Effects of RAGE-Ig Fusion Protein on Early Diabetic Retinopathy and Tactile Allodynia
Abstract Number: 1004-P
Authors: TIMOTHY S. KERN, GUANYUAN LI, JIE TANG, YUNPENG DU, CHIEH A. LEE
Institutions: Cleveland, OH
Results: RAGE (Receptor for Advanced Glycation Endproducts) has been implicated in the pathogenesis of numerous complications of diabetes. We assessed the effect of a novel RAGE fusion protein inhibitor on retinal histopathology and nerve function, and on retinal inflammation and oxidative stress. C57BL/6J mice were made diabetic with streptozotocin, and some were given a RAGE fusion protein (10, 100, or 300 µg per mouse). Mice were sacrificed at 2 mos and 10 mos of study for assessment of retinal vascular histopathology, accumulation of albumin in neural retina, cell loss in ganglion cell layer, and biochemical and physiological abnormalities in retina. Tactile allodynia was measured on a paw at 8-9 mos diabetes. Leukostasis, expression of ICAM, accumulation of albumin in neural retina, nitration of retinal proteins were significantly increased in retinas of mice diabetic for 2 months, and the number of degenerate retinal capillaries was significantly increased in mice diabetic for 10 months compared to nondiabetic controls. Diabetes also enhanced sensitivity of peripheral nerves to light touch (tactile allodynia). All three doses of the RAGE fusion protein inhibited capillary degeneration, accumulation of albumin in the neural retina, nitration of retinal proteins, and tactile allodynia. In contrast, leukostasis and ICAM expression were not normalized by doses of drug that normalized the histopathology. RAGE plays an important role in the pathogenesis of vascular lesions characteristic of early diabetic retinopathy and in sensory nerve dysfunction in diabetic mice, and the beneficial effects of the drug tested on the retinal vasculature seem not mediated via leukostasis.