IgG4-ROD是累及眼眶的免疫相关纤维炎症性疾病，晚期严重影响视功能甚至失明。以往研究发现该病纤维化程度越高复发率越高，对激素等治疗敏感性越低。因此聚焦于该病纤维化的研究是揭示其发生和寻找有效治疗方法的关键。项目组前期利用IgG4-ROD组织标本及LatY136F敲入小鼠模型发现Smo、STAT3、p-STAT3、TIMP-1显著高表达且超声响应性载环杷明微囊定向控释能通过抑制Smo降低Stat3, p-Stat3/Timp-1表达。据此本项目提出Smo通过调控STAT3影响TIMP1表达抑制纤维化的研究假设。本项目拟采用载环杷明微囊定向作用于LatY136F敲入小鼠泪腺，探究其对IgG4-ROD泪腺纤维化进程的抑制作用，并结合紫外交联免疫沉淀结合高通量测序等技术全面辨析介导Smo与STAT3相互作用的关键蛋白及RNA，以期为以纤维化为特点的IgG4-ROD提供全新的理论依据和治疗方案。

IgG4-related ophthalmic disease（IgG4-ROD）is an immune-related fibrous inflammatory disease involving the eyelids, which seriously affects visual function and even blindness. Previous studies have found that the higher the degree of fibrosis, the higher the recurrence rate, and the lower the sensitivity to hormones treatment. Therefore, the research focusing on fibrosis of the disease is the key to revealing its occurrence and finding effective treatments. In preliminary work, we have found that Smo, STAT3, p-STAT3, TIMP-1 were highly expressed in both IgG4-ROD tissue samples and LatY136F knock-in mouse model, and we also found the directional controlled release of ultrasonically responsive cyclopamine-microcapsules could decreased Stat3, p-Stat3/Timp-1 expressions by inhibiting Smo expression. Based on these findings, we propose the hypothesis that Smo inhibits TIMP-1 expression by regulating STAT3 so that inhibiting the fibrosis of the IgG4-ROD. In this project, we aim to use the cyclopamine-microcapsule to directly act on the lacrimal gland of LatY136F knock-in mice to explore its inhibitory effect on the process of IgG4-ROD lacrimal fibrosis, and comprehensively analyze the key proteins and RNAs that mediate the interaction between Smo and STAT3 with the techniques of crosslinking-immunprecipitation and high-throughput sequencing, as well as provide a new theoretical basis and treatment plan for IgG4-ROD characterized by fibrosis inflammation.