Department of Ophthalmology, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, the First Affiliated Hospital of Chongqing Medical University, No.1 You Yi Road, Yu Zhong District, Chongqing, 400016, China.
BMC Pharmacol Toxicol. 2020 Feb 4;21(1):9. doi: 10.1186/s40360-020-0387-6.
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.
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 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.
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.
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.
环孢素 A 已被视为治疗各种免疫炎症性疾病的免疫调节剂和抗炎药物。然而，环孢素 A 对 2 型糖尿病大鼠视网膜的影响及其潜在机制仍有待阐明。本研究旨在探讨环孢素 A 对糖尿病视网膜病变的作用及机制。
雄性 Sprague-Dawley 大鼠建立 2 型糖尿病模型。6 周后，糖尿病大鼠和正常对照组分别向左眼玻璃体内注射环孢素 A（42ng/2μL），右眼注射 2μL DMSO 作为对照。另一组正常野生型大鼠左眼分别玻璃体注射 5μL PBS 或 HMGB-1（5ng/5μL）或 HMGB-1（5ng/5μL）加环孢素 A（42ng/2μL）。用苏木精-伊红染色观察视网膜形态变化。免疫组织化学、ELISA 或 Western blot 或 RT-PCR 检测 HMGB-1、IL-1β和 TNF-α的表达。
2 型糖尿病大鼠和玻璃体内注射 HMGB-1 的正常大鼠视网膜中 IL-1β和 TNF-α的表达上调，玻璃体内注射环孢素 A 可减弱其表达。此外，环孢素 A 降低了糖尿病大鼠视网膜中 HMGB-1 的表达，缓解了 2 型糖尿病大鼠的视网膜病变。
玻璃体内给予环孢素 A 对糖尿病大鼠的视网膜具有保护作用，可能通过抑制 HMGB-1 来下调 IL-1β和 TNF-α在视网膜中的表达。
