Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, China.
Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, China,
Ophthalmic Res. 2020;63(4):434-442. doi: 10.1159/000505003. Epub 2019 Nov 26.
To demonstrate the anti-inflammatory action of a synthetic glucocorticoid-induced leucine zipper (GILZ98-134) peptide (GILZ-p) in a model of endotoxin-induced uveitis (EIU) in rats.
The EIU model was induced in Sprague Dawley rats with an intravitreal injection of lipopolysaccharide (LPS). Synthetic GILZ-p was injected intravitreally 6 h after the LPS injection. To evaluate the anti-inflammatory effects of GILZ-p, the inflammatory response in the anterior chamber and iris of the rat eyes was evaluated with a slitlamp microscope on days 0, 1, 2, 3, and 4 after GILZ-p injection. The retinal expression of inflammatory cytokines was measured on days 0, 1, 2, 3, and 4 after GILZ-p injection. Müller cell gliosis was also detected at planned time points after GILZ-p injection.
Anterior segment inflammation peaked at 24 h after LPS injection in the EIU model. Compared with the controls, intravitreal GILZ-p significantly suppressed LPS-induced anterior segment inflammation in the EIU rats. The levels of retinal inflammatory factors IL-1β, TNF-α, MCP-1, and ICAM-1 were simultaneously reduced by the intravitreal GILZ-p injection. The expression of vimentin in the EIU retina was significantly reduced by GILZ-p, and the downregulated aquaporin 4 in the EIU retina was significantly restored by GILZ-p.
The synthetic GILZ-p inhibited the inflammatory reaction in the EIU model and may have utility in the treatment of inflammatory ocular disease.
在大鼠内毒素性葡萄膜炎（EIU）模型中，展示一种合成的糖皮质激素诱导亮氨酸拉链（GILZ98-134）肽（GILZ-p）的抗炎作用。
通过玻璃体内注射脂多糖（LPS）在 Sprague Dawley 大鼠中诱导 EIU 模型。在 LPS 注射后 6 小时，玻璃体内注射合成的 GILZ-p。为了评估 GILZ-p 的抗炎作用，在 GILZ-p 注射后第 0、1、2、3 和 4 天，通过裂隙灯显微镜评估大鼠眼前房和虹膜的炎症反应。在 GILZ-p 注射后第 0、1、2、3 和 4 天，测量视网膜中炎症细胞因子的表达。在 GILZ-p 注射后的预定时间点，还检测了 Müller 细胞胶质增生。
在 EIU 模型中，LPS 注射后 24 小时前节炎症达到高峰。与对照组相比，玻璃体内 GILZ-p 显著抑制了 EIU 大鼠的 LPS 诱导的前节炎症。玻璃体内 GILZ-p 注射同时降低了视网膜炎症因子 IL-1β、TNF-α、MCP-1 和 ICAM-1 的水平。EIU 视网膜中的波形蛋白表达显著减少，GILZ-p 显著恢复了 EIU 视网膜中下调的水通道蛋白 4。
合成的 GILZ-p 抑制了 EIU 模型中的炎症反应，可能对治疗炎症性眼病有一定的应用价值。
