Department of Ophthalmology, Chonnam National University Medical School and Hospital, Gwangju, South Korea.
Allysta Pharmaceuticals, Belmont, California.
J Ocul Pharmacol Ther. 2020 Mar;36(2):88-96. doi: 10.1089/jop.2018.0131. Epub 2019 Oct 30.
To evaluate the efficacy of adiponectin (APN)-derived short peptides (ADPs) 355 compared with globular APN in a mouse model of experimental dry eye (EDE) and corneal alkali burn. EDE and chemical burn were induced in C57BL/6 mice by desiccating stress and application of NaOH, respectively. Eye drops consisting of 0.01% globular APN, 0.01% ADPs, 0.1% ADPs, or balanced salt solution (BSS) were applied. Tear volume, tear film break-up time, and corneal staining scores were measured. Concentrations of interleukin (IL)-1β, interferon (IFN)-γ, IL-6, CXCL-9, and CXCL-10 using multiplex immunobead assay were evaluated, and flow cytometry were performed. Corneal epithelial defects and haze degree were analyzed, and enzyme-linked immunosorbent assay for IL-1β and transforming growth factor (TGF)-β levels were observed. All treatment groups showed an improvement in clinical parameters and CD4+CCR5+ T cell and CD11b+ cell infiltrations in the conjunctiva (all < 0.05). Both ADPs groups had significantly decreased concentrations of IL-1β, IFN-γ, IL-6, CXCL-9, and CXCL-10 in the conjunctiva than the EDE or BSS group. Significantly improved parameters of epithelial defect, degree of haze, and concentrations of IL-1β and TGF-β were observed in all treatment groups. However, no significant differences were noted in clinical or experimental parameters among treatment groups. Topical ADPs could effectively improve clinical signs and inflammation of ocular surface in the EDE or alkali burn, and its efficacy and potency were similar to those of globular APN.
为了评估脂联素（APN）衍生短肽（ADPs）355 与球状 APN 在实验性干眼症（EDE）和角膜碱烧伤小鼠模型中的疗效。通过干燥应激和应用 NaOH 分别在 C57BL/6 小鼠中诱导 EDE 和化学烧伤。应用含有 0.01%球状 APN、0.01%ADPs、0.1%ADPs 或平衡盐溶液（BSS）的眼药水。测量泪液体积、泪膜破裂时间和角膜染色评分。使用多重免疫珠测定法评估白细胞介素（IL）-1β、干扰素（IFN）-γ、IL-6、CXCL-9 和 CXCL-10 的浓度，并进行流式细胞术。分析角膜上皮缺损和混浊程度，并观察 IL-1β 和转化生长因子（TGF）-β 水平的酶联免疫吸附试验。所有治疗组的临床参数均有改善，CD4+CCR5+T 细胞和结膜浸润的 CD11b+细胞（均<0.05）。与 EDE 或 BSS 组相比，ADPs 组结膜中的 IL-1β、IFN-γ、IL-6、CXCL-9 和 CXCL-10 浓度均显著降低。所有治疗组的上皮缺损参数、混浊程度、IL-1β 和 TGF-β 浓度均显著改善。然而，治疗组之间的临床或实验参数无显著差异。局部 ADPs 可有效改善 EDE 或碱烧伤的眼表临床症状和炎症，其疗效和效力与球状 APN 相似。
