Abstract
BackgroundCyclosporine-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.MethodsMale 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 2 μL 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 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 or RT-PCR.ResultsRetinal 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.ConclusionsIntravitreal 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.
Highlights
Cyclosporine-A has been regarded as an immunoregulatory and anti-inflammatory drug for the treatment of various immune inflammatory diseases
Immunohistochemical detection and the protein expression of high mobility group box-1 (HMGB-1) Location and expression level of HMGB-1 in the retinal tissues were determined by immunohistochemistry and western blot methods
Specific inhibitor or genetic deficiency of tumor necrosis factor-α (TNF-α) greatly reduced the leukocyte adhesion and blood-retinal barrier breakdown in the diabetic retina [5, 24]. In agreement with these studies, we demonstrated a significant upregulation of IL-1β and TNF-α in the six-week diabetic rat retina, and that intravitreal administration of Cs-A significantly decreased this upregulation induced by diabetes
Summary
Cyclosporine-A has been regarded as an immunoregulatory and anti-inflammatory drug for the treatment of various immune inflammatory diseases. 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. A few studies show that Cs-A has a protective effect on the retina of streptozotocin (STZ)-induced diabetic rats, possibly through impeding the immunoglobulins deposition [11] or reducing the bloodretinal barrier permeability [12] in the diabetic retina. Little has been known about the impact of Cs-A on the retina of type 2 diabetic rats and the underlying mechanism. The aim of our study was to investigate the effect of Cs-A on the retinopathy in a type 2 DM animal model and to elucidate its potential mechanism, to study the alternation of expression levels of HMGB-1, IL-1β and TNF-α in the retinal tissues
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