Sande P H, Dorfman D, Fernandez D C, Chianelli M, Domínguez Rubio A P, Franchi A M, Silberman D M, Rosenstein R E, Sáenz D A
Laboratory of Retinal Neurochemistry and Experimental Ophthalmology, Department of Human Biochemistry, School of Medicine/CEFyBO, University of Buenos Aires/CONICET, Buenos Aires, Argentina.
Br J Pharmacol. 2014 Dec;171(24):5696-707. doi: 10.1111/bph.12873.
Uveitis is a prevalent intraocular inflammatory disease and one of the most damaging ocular conditions. Pretreatment with melatonin prevented ocular inflammation induced by an intravitreal injection of bacterial LPS in the Syrian hamster. Here, we have assessed the anti-inflammatory effects of melatonin administered after the onset of ocular inflammation.
The eyes of male Syrian hamsters were intravitreally injected with vehicle or LPS. Melatonin was injected i.p. every 24 h, starting 12 or 24 h after the LPS injection. A clinical evaluation (with a score index based on clinical symptoms), the number of infiltrating cells, protein concentration and PGE2 and PGF2α levels in the aqueous humour, as well as retinal NOS activity, lipid peroxidation and TNF-α levels were assessed. Retinal function was assessed by scotopic electroretinography, and light microscopy and immunohistochemistry were used to evaluate the state of the retinal structure.
Both treatment regimens with melatonin decreased clinical symptoms, reduced the leakage of cells and proteins, and decreased PG levels in aqueous humour from eyes injected with LPS. In addition, melatonin treatment blocked the decrease in scotopic electroretinogram a- and b-wave amplitude, protected the retinal structure and reduced the increase in NOS activity, lipid peroxidation and TNF-α levels, induced by LPS.
These results indicate that treatment with melatonin, starting after the onset of uveitis, attenuated ocular inflammation induced by LPS in the Syrian hamster and support the use of melatonin as a therapeutic resource for uveitis treatment.
葡萄膜炎是一种常见的眼内炎症性疾病,也是最具破坏性的眼部疾病之一。褪黑素预处理可预防叙利亚仓鼠玻璃体内注射细菌脂多糖(LPS)诱导的眼部炎症。在此,我们评估了眼部炎症发作后给予褪黑素的抗炎作用。
给雄性叙利亚仓鼠的眼睛玻璃体内注射溶剂或LPS。从LPS注射后12或24小时开始,每24小时腹腔注射一次褪黑素。评估临床症状(基于临床症状的评分指数)、浸润细胞数量、房水中蛋白质浓度以及PGE2和PGF2α水平,以及视网膜NOS活性、脂质过氧化和TNF-α水平。通过暗视视网膜电图评估视网膜功能,并用光学显微镜和免疫组织化学评估视网膜结构状态。
两种褪黑素治疗方案均减轻了临床症状,减少了细胞和蛋白质渗漏,并降低了注射LPS的眼睛房水中的PG水平。此外,褪黑素治疗阻止了暗视视网膜电图a波和b波振幅的降低,保护了视网膜结构,并减少了LPS诱导的NOS活性、脂质过氧化和TNF-α水平的升高。
这些结果表明,葡萄膜炎发作后开始用褪黑素治疗,可减轻叙利亚仓鼠中LPS诱导的眼部炎症,并支持将褪黑素用作葡萄膜炎治疗的一种治疗手段。