Cyclosporine-A Attenuates Retinal Inflammation by Inhibiting HMGB-1 Formation in Rats with Type 2 Diabetes Mellitus
Abstract Background:Cyclosporine-A has been regarded as an immunoregulatory and anti-inflammatory drug for the treatment of various immune inflammatory diseases. However, the effect of Cyclosporine-A on the retina of type 2 diabetic rats and the underlying mechanism remains to be elucidated. The objective of the present study was to investigate the effect and mechanism of Cyclosporine-A on diabetic retinopathy. Methods:Male Sprague-Dawley rats were established to type 2 diabetic model.After 6 weeks, diabetic rats and normal controls were intravitreally injected with Cs-A (42 ng/2 μL) to the left eye, and 2μL DMSO to the right eye for the control. Another part of normal wild-type rats was subjected to intravitreal injections into the left eyes with 5 μL PBS or HMGB-1 (5 ng/5 μL) or HMGB-1(5 ng/5 μL) plus Cs-A (42 ng/2 μL), respectively. Retinal morphological changes were observed with hematoxylin–eosin staining. Expressions of HMGB-1, IL-1β and TNF-α were detected by immunohistochemistry, ELISA or western blot. Results:Retinal expression levels of IL-1β and TNF-α were upregulated in type 2 diabetic rats and in normal rats with intravitreal injection of HMGB-1, which were attenuated by intravitreal Cs-A. Moreover, Cs-A decreased HMGB-1 expression in diabetic retina and relieved the retinopathy in type 2 diabetic rats. Conclusions:Intravitreal administration of Cs-A showed a protective effect on retina of diabetic rats, possibly by downregulating retinal expressions of IL-1β and TNF-α via the suppression of HMGB-1.