Agarwal Aniruddha, Rajagopalan Nithya, Hassan Muhammad, Sadiq Mohammad Ali, Soliman Mohamed K, Afridi Rubbia, Sepah Yasir Jamal, Nguyen Quan Dong
Dev Ophthalmol. 2016;55:276-81. doi: 10.1159/000438951. Epub 2015 Oct 26.
Chronic inflammation plays an important role in the pathogenesis of ocular diseases such as diabetic retinopathy, uveitis and age-related macular degeneration. Activation and proliferation of naïve T cells may result in pathological changes responsible for significant visual morbidity. Sirolimus (earlier termed rapamycin) is a novel drug that inhibits cellular kinases and, thereby, inhibits T-cell proliferation. Preclinical studies in experimental models have shown promising results with the use of this pharmacological agent in various ocular conditions. Subsequently, early phase I/II studies have provided encouraging safety and efficacy data. This chapter focuses on the mechanisms of action, preclinical study results and data from human clinical trials of sirolimus in human eye diseases. Key highlights from ongoing phase III clinical trials are also provided. Sirolimus, thus, appears to be an important addition to the armamentarium of steroid-sparing therapeutic agents that act on various steps in the inflammatory pathway.
慢性炎症在糖尿病视网膜病变、葡萄膜炎和年龄相关性黄斑变性等眼部疾病的发病机制中起重要作用。幼稚T细胞的激活和增殖可能导致造成严重视觉损害的病理变化。西罗莫司（早期称为雷帕霉素）是一种新型药物，可抑制细胞激酶，从而抑制T细胞增殖。在实验模型中的临床前研究表明，在各种眼部疾病中使用这种药物具有良好前景。随后，早期的I/II期研究提供了令人鼓舞的安全性和有效性数据。本章重点介绍西罗莫司在人类眼部疾病中的作用机制、临床前研究结果以及人体临床试验数据。还提供了正在进行的III期临床试验的关键要点。因此，西罗莫司似乎是作用于炎症途径各个环节的类固醇节省治疗药物库中的重要补充。
