Moreira Castro Brenda Fernanda, Nunes da Silva Carolina, Barbosa Cordeiro Lídia Pereira, Pereira de Freitas Cenachi Sarah, Vasconcelos-Santos Daniel Vitor, Machado Renes Resende, Dias Heneine Luiz Guilherme, Silva Luciana Maria, Silva-Cunha Armando, Fialho Silvia Ligório
Faculty of Pharmacy, Federal University of Minas Gerais, 6627 Presidente Antônio Carlos Avenue, Pampulha, Belo Horizonte, Minas Gerais, 31270-901, Brazil.
Department of Chemistry, Federal University of Minas Gerais, 6627 Presidente Antônio Carlos Avenue, Pampulha, Belo Horizonte, Minas Gerais, 31270-901, Brazil.
Curr Res Pharmacol Drug Discov. 2022 May 11;3:100107. doi: 10.1016/j.crphar.2022.100107. eCollection 2022.
Uveitis is a group of sight-threatening ocular inflammatory disorders, whose mainstay of therapy is associated with severe adverse events, prompting the investigation of alternative treatments. The peptide melittin (MEL) is the major component of bee venom and presents anti-inflammatory and antiangiogenic activities, with possible application in ophthalmology. This work aims to investigate the potential of intravitreal MEL in the treatment of ocular diseases involving inflammatory processes, especially uveitis. Safety of MEL was assessed in retinal cells, chick embryo chorioallantoic membranes, and rats. MEL at concentrations safe for intravitreal administration showed an antiangiogenic activity in the chorioallantoic membrane model comparable to bevacizumab, used as positive control. A protective anti-inflammatory effect in retinal cells stimulated with lipopolysaccharide (LPS) was also observed, without toxic effects. Finally, rats with bacille Calmette-Guerin- BCG) induced uveitis treated with intravitreal MEL showed attenuated disease progression and improvement of clinical, morphological, and functional parameters, in addition to decreased levels of proinflammatory mediators in the posterior segment of the eye. These effects were comparable to the response observed with corticosteroid treatment. Therefore, MEL presents adequate safety profile for intraocular administration and has therapeutic potential as an anti-inflammatory and antiangiogenic agent for ocular diseases.
葡萄膜炎是一组威胁视力的眼部炎症性疾病，其主要治疗方法会引发严重不良事件，这促使人们对替代治疗方法展开研究。蜂毒肽（MEL）是蜂毒的主要成分，具有抗炎和抗血管生成活性，在眼科领域可能具有应用价值。这项研究旨在探究玻璃体内注射MEL治疗涉及炎症过程的眼部疾病，尤其是葡萄膜炎的潜力。研究评估了MEL在视网膜细胞、鸡胚绒毛尿囊膜和大鼠中的安全性。玻璃体内注射安全浓度的MEL在绒毛尿囊膜模型中显示出与用作阳性对照的贝伐单抗相当的抗血管生成活性。在脂多糖（LPS）刺激的视网膜细胞中也观察到了保护性抗炎作用，且无毒性作用。最后，玻璃体内注射MEL治疗卡介苗（BCG）诱导的葡萄膜炎大鼠，除了眼后段促炎介质水平降低外，还显示出疾病进展减缓以及临床、形态和功能参数的改善。这些效果与皮质类固醇治疗所观察到的反应相当。因此，MEL在眼内给药时具有足够的安全性，并且作为眼部疾病的抗炎和抗血管生成药物具有治疗潜力。
