点状内层脉络膜病变的肉芽肿性炎症病因学初探

Punctate inner choroidopathy (PIC) is a myopia-associated chorioretinitis and the first cause of the inflammation-induced choroidal neovascularization. Our previous study established an international staging system for PIC lesion based on the observation of the natural history of PIC, and revealed that PIC was a granulomatous inflammation possibly attacking the photoreceptor layer. In our preliminary experiment, a Th1-predominant cytokine expression profile in serum was found from the active PIC patients, indicating a systemic immune abnormity in this local ocular disease. Etiologic study for PIC is in blank basically. This study is designed to identify the cause of PIC by two vital clues, the granulomatous inflammation and the myopia association. The study content includes (1) the association between the progression rate and a variety of biometric data of myopia and the onset and relapse of PIC; (2) the existence of DNA and antibodies of the infectious granuloma triggers such as Histoplasma capsulatum, and myopia-associated autoantigens and autoantibodies in peripheral blood and aqueous humor; (3) the spectrum of peripheral blood mononuclear cells and its response to myopia-associated autoantigens, and expression profile of cytokines at each stage of PIC; (4) the association between HLA typing and PIC. This initial etiologic exploration for PIC will answer the question whether PIC is an infectious or autoimmune disease, and whether the associated myopia is an anatomic facilitation or an autoantigen provider for the disease development, and give a scientific basis for the intervention, prevention and control of PIC.

点状内层脉络膜病变（PIC）是与近视显著相关的视网膜脉络膜炎，是炎症相关性脉络新生血管的第一大原因。我们前期通过PIC的自然病程观察，建立了病灶的国际标准分期，并指出其本质是以光感受器层为可能攻击靶标的肉芽肿性炎症。预实验表明活动性PIC患者外周血有系统性免疫指标异常，血清细胞因子呈Th1表达优势。PIC病因学研究基本空白；本项目围绕肉芽肿性炎症和近视相关性两个关键线索，初步对其进行病因学探索：分析PIC临床发病和复发与近视进展率及其各类生物测量数据的关联性；外周血和房水中检测近视相关自身抗原，搜寻组织胞浆菌等4种临床表现类似PIC的致肉芽肿性微生物感染的证据；研究PIC不同病程外周血T细胞亚群异常的特征和细胞因子频谱变化以及对近视自身抗原刺激的反应；调查PIC与HLA基因分型的关联性。拟回答PIC是感染性或自身免疫性疾病，近视是其解剖学发病基础还是自身抗原来源，为PIC防治提供科学依据。

点状内层脉络膜病变（PIC）是与近视显著相关的视网膜脉络膜炎，是炎症相关性脉络膜新生血管的第一大原因。本项目研究显示PIC的结节病灶与肉芽肿性葡萄膜炎的交感性眼炎和Vogt-小柳-原田综合征中Dalén-Fuchs结节具有相同的影像和临床病程特征，提示PIC病灶可能是后极部的Dalén-Fuchs肉芽肿结节；通过对164名近视患者的随访发现PIC是近视患者黄斑区和视盘旁局灶视网膜脉络膜萎缩的首要原因，同时PIC肉芽肿性炎症退行中可产生两种类型类似于囊样水肿的非活动性视网膜内囊腔。对50岁以下人群脉络膜新生血管病因调查中显示PIC是国人青壮年脉络膜新生血管的三大主要原因之一，血管内皮生长因子仍然是PIC肉芽肿性炎症继发脉络膜新生血管的主要促进因素并可作为治疗靶标取得较好治疗效果。PIC患者血清中未发现致肉芽肿性微生物感染证据。综合初步结果提示近视相关的局部自身免疫反应可能是PIC主要发病机制。