雷帕霉素治疗非感染性葡萄膜炎的研究现状与进展

Current state and progress of rapamycin in the treatment of non-infectious uveitis

糖皮质激素(GCS)是大多数非感染性葡萄膜炎(NIU)的主要治疗药物。但长期全身使用GCS会导致患者出现高血压、高血脂和糖尿病等全身副作用,局部使用GCS也可导致患眼白内障、眼压升高或青光眼。雷帕霉素(RAPA)具有免疫抑制、抗血管生成、抗增生等作用,目前的动物实验和临床试验研究均表明其在治疗NIU方面具有一定的潜力,尤其是玻璃体腔注射这种治疗方式,可将患者的全身暴露降至最小,并减少不良事件的发生。但同时我们也应关注其全身应用的不良反应。近年来,有研究试图采用纳米结构载体包括胶束、脂质体、纳米晶体、聚合物纳米颗粒和磁性纳米颗粒等增强RAPA制剂的穿透力以及治疗眼后节疾病的疗效。这些药物载体是否可以装载RAPA用于NIU的治疗,值得进一步研究和探索。

Glucocorticoids(GCS)are the main treatment for non-infectious uveitis(NIU).However,long-term GCS treatment may induce systemic side effects including hypertension,hyperlipidemia and diabetes.Patients may develop cataract,ocular hypertension or glaucoma because of topical application of GCS.Rapamycin(RAPA)exhibits immunosuppressive,antiangiogenic and antiproliferative effects.Animal experiments and clinical trials have shown that RAPA has therapeutic potential for NIU,especially the treatment of intravitreal injection.In particular,intravitreal injection of RAPA can result in minimal systemic exposure and reduce adverse events.Meanwhile,systemic unwanted effects should be concerned about.In recent years,some studies have attempted to employ nanostructured carriers to improve penetrating abilities of RAPA and efficacy of treatment for ocular posterior segment diseases.These carriers include micelles,liposomes,nanocrystals,polymeric nanoparticles,magnetic nanoparticles and so on.Whether they can load RAPA for treating NIU deserves further study and exploration.