Cyclosporine-a attenuates retinal inflammation by inhibiting HMGB-1 formation in rats with type 2 diabetes mellitus

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 mu L) to the left eye, and 2 mu L DMSO to the right eye for the control.. Another group of normal wild-type rats was subjected to intravitreal injections into. The left eyes with 5 mu L PBS or HMGB-1 (5 ng/5 mu L) or HMGB-1(5 ng/5 mu L) plus. Cs-A (42 ng/2 mu L), respectively. Retinal morphological changes were observed with. Hematoxylin-eosin staining. Expressions of HMGB-1, IL-1 beta and TNF-alpha were. Detected by immunohistochemistry, ELISA or Western blot or RT-PCR. Results Retinal expression levels of IL-1 beta and TNF-alpha 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-1 beta and TNF-alpha. via the suppression of HMGB-1.