Mérida Salvador, Sancho-Tello María, Almansa Inmaculada, Desco Carmen, Peris Cristina, Moreno Mari-Luz, Villar Vincent M, Navea Amparo, Bosch-Morell Francisco
Departamento de Ciencias Biomédicas, Instituto de Ciencias Biomédicas, Universidad Cardenal Herrera-CEU, CEU Universities, Valencia, Spain.
Department of Pathology, University of Valencia, Valencia, Spain.
Front Pharmacol. 2018 Jun 19;9:649. doi: 10.3389/fphar.2018.00649. eCollection 2018.
Uveitis is an eye disease characterized by inflammation of the uvea and an early and exhaustive diagnosis is essential for its treatment. The aim of our study is to assess the potential toxicity and anti-inflammatory efficacy of Bevacizumab in an experimental uveitis model by subcutaneously injecting lipopolysaccharide into Lewis rats and to clarify its mechanism. Blood-aqueous barrier integrity was assessed 24 h after endotoxin-induced uveitis (EIU) by analyzing two parameters: cell count and protein concentration in aqueous humors. Histopathology of all eye structures was also studied. Enzyme-linked immunosorbent analyses of the aqueous humor samples were performed in order to calculate the diverse chemokine and cytokine protein levels and oxidative stress-related markers were also evaluated. The aqueous humor's cellular content significantly increased in the group treated with only Bevacizumab, but it had no effect on retina histopathological grading. Nevertheless, the inflammation noted in ocular structures when administering Bevacizumab with endotoxin was mostly prevented since aqueous humor cell content considerably lowered, and concomitantly with a sharp drop in uveal, vitreous, and retina histopathological grading. The values of the multi-faceted cytokine IL-2 also significantly decreased ( < 0.05 vs. endotoxin group), and the protective IL-6 and IL-10 cytokines values rose with related anti-oxidant system recovery ( < 0.05 vs. endotoxin group). Concurrently, some related M1 macrophage chemokines substantially increased, e.g., GRO/KC, a chemokine that also displays any kind of protective role. All these results revealed that 24 h after being administered, Bevacizumab treatment in EIU significantly prevented inflammation in various eye structures and correct results in efficacy vs. toxicity balance were obtained.
葡萄膜炎是一种以葡萄膜炎症为特征的眼部疾病,早期进行详尽诊断对其治疗至关重要。我们研究的目的是通过向Lewis大鼠皮下注射脂多糖建立实验性葡萄膜炎模型,评估贝伐单抗的潜在毒性和抗炎疗效,并阐明其作用机制。在内毒素诱导的葡萄膜炎(EIU)24小时后,通过分析房水中的两个参数:细胞计数和蛋白质浓度,评估血-房水屏障的完整性。还研究了所有眼部结构的组织病理学。对房水样本进行酶联免疫吸附分析,以计算多种趋化因子和细胞因子的蛋白质水平,并评估氧化应激相关标志物。仅用贝伐单抗治疗的组中,房水细胞含量显著增加,但对视网膜组织病理学分级没有影响。然而,当贝伐单抗与内毒素联合给药时,眼部结构中的炎症大多得到预防,因为房水细胞含量大幅降低,同时葡萄膜、玻璃体和视网膜组织病理学分级也急剧下降。多方面细胞因子IL-2的值也显著降低(与内毒素组相比,P<0.05),具有保护作用的IL-6和IL-10细胞因子的值随着相关抗氧化系统的恢复而升高(与内毒素组相比,P<0.05)。同时,一些相关的M1巨噬细胞趋化因子大幅增加,例如GRO/KC,这种趋化因子也发挥着某种保护作用。所有这些结果表明,在EIU模型中给药24小时后,贝伐单抗治疗可显著预防各种眼部结构的炎症,并在疗效与毒性平衡方面取得了正确的结果。