Cai Maoyu, Xu Zunkai, Zhou Xueyan, Li Liangpin, Hua Xia, Guo Shutao, Yuan Xiaoyong
Clinical College of Ophthalmology, Tianjin Medical University, Tianjin 300020, China
Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin Eye Institute, Tianjin Eye Hospital, Tianjin 300020, China
APL Bioeng. 2022 Oct 26;6(4):046101. doi: 10.1063/5.0118311. eCollection 2022 Dec.
Corticosteroids have for some time been used as first-line drugs for the topical treatment of noninfectious uveitis, but poor ocular bioavailability and the rapid clearance of eye drops necessitate frequent dosing, reducing patient compliance. In this study, we used an acid-sensitive stearoxyl-ketal-dexamethasone pro-drug microcrystals (SKD MCs), which is consistently safe and effective in the control of uveitis inflammation in rats. We used a rat model of experimental autoimmune uveitis (EAU) to evaluate the effects of SKD MCs in terms of clinical manifestations, molecular biology, pathological histology, and visual electrophysiology compared to dexamethasone sodium phosphate injection or phosphate-buffered saline. SKD MCs significantly reduced inflammation in EAU, improved the ability to suppress inflammatory cytokines and to protect retinal function, and significantly reduced retinal microglia activation, with no increase in intraocular pressure throughout the treatment. Our results indicate that the SKD MCs formulation holds promise as a new strategy for the treatment of noninfectious uveitis and potentially other ocular inflammatory diseases.
一段时间以来，皮质类固醇一直被用作非感染性葡萄膜炎局部治疗的一线药物，但眼部生物利用度差以及眼药水的快速清除需要频繁给药，从而降低了患者的依从性。在本研究中，我们使用了一种酸敏硬脂酰氧基缩酮 - 地塞米松前药微晶（SKD MCs），其在控制大鼠葡萄膜炎炎症方面始终安全有效。我们使用实验性自身免疫性葡萄膜炎（EAU）大鼠模型，与地塞米松磷酸钠注射液或磷酸盐缓冲盐水相比，从临床表现、分子生物学、病理组织学和视觉电生理学方面评估SKD MCs的效果。SKD MCs显著减轻了EAU中的炎症，提高了抑制炎性细胞因子和保护视网膜功能的能力，并显著降低了视网膜小胶质细胞的活化，在整个治疗过程中眼压没有升高。我们的结果表明，SKD MCs制剂有望成为治疗非感染性葡萄膜炎以及潜在的其他眼部炎症性疾病的新策略。
