IMMUNOPATHOLOGY IN EYES WITH EXPERIMENTAL AND CLINICAL OCULAR DISEASES

采用免疫组织化学、原位杂交、聚合酶链式反应和显微解剖等方法，对患者标本和各种实验性葡萄膜炎动物模型中细胞及其标志物的定位和定位进行分析。1999财年，我们完成了以下4个研究课题：1.原代眼内淋巴瘤细胞基因和蛋白质的检测。利用显微解剖和聚合酶链式反应技术，我们将一些感染性病原体的存在与原发性眼内淋巴瘤联系起来。我们进一步报道了B细胞淋巴瘤、玻璃体内IL-10水平和IL-10/IL-6比值之间的关系，这可以提高对该肿瘤的诊断率。HTLV-1感染与T细胞白血病/淋巴瘤本研究采用显微解剖和聚合酶链式反应技术，对HTLV-1相关T细胞白血病/淋巴瘤中HTLV-1病毒基因和T细胞受体基因重排进行了研究和论证。3.内毒素诱导葡萄膜炎的发病机制。应用酶联免疫吸附试验和逆转录聚合酶链式反应技术，研究了小鼠EIU中细胞因子的动态变化及病理变化。我们发现，这种疾病与眼睛中的各种细胞因子水平密切相关，特别是IL-6。在最敏感的C3H/HEN株中，眼部对内毒素的炎症反应是双相性的。相反，在其他患有EIU的小鼠中，眼部炎症是单相的，没有两种细胞因子波。4.过敏性结膜炎的调节。在豚草(RW)诱导的小鼠过敏性结膜炎模型中，免疫刺激DNA序列(ISS)可以抑制正在进行的Th2/过敏反应，并诱导从头开始的Th1反应。RW致敏后的全身或局部ISS可抑制即刻超敏反应和晚期细胞浸润，并诱导RW特异性Th1反应。ISS可能为眼部过敏的当前标准护理提供另一种选择。

The identity and topographic localization of cells and their markers in patient samples and various experimental uveitis animal models were analyzed by immunohistochemistry, in situ hybridization, polymerase chain reaction (PCR), and microdissection. In FY1999 we have complished the following 4 research topics: 1. Detection of Genes and Proteins in Primary Intraocular Lymphoma Cells. Using microdissection and PCR techniques we linked the presence of some infectious agents and primary intraocular lymphoma. We further reported the association between B-cell lymphoma, intravitreal IL-10 level and IL-10:IL-6 ratio and that could improve the diagnostic yield for this tumor.2. HTLV-1 Infection and T cell leukemia/lymphoma. Using microdissection and PCR, we studied and demonstrated HTLV-1 viral genes and T cell receptor gene rearangements in HTLV-1 associated T-cell leukemia/lymphoma. 3. Pathogenesis of Endotoxin-Induced Uveitis (EIU). Using ELISA and RT-PCR, we studied the kinetics of cytokines and pathology in murine EIU. We found that the disease is closely related to various cytokine levels, particularly IL-6, in the eye. Ocular inflammatory response to LPS is biphasic in the most susceptible strain, C3H/HeN. In contrast, ocular inflammation is monophasic without two cytokine waves in other murine strains with EIU. 4. Modulation of Allergic Conjunctivitis. We showed that immunostimulatory DNA sequences (ISS) can inhibit an on-going Th2/allergic response and induce a de novo Th1 response in the ragweed (RW)-induced murine allergic conjunctivitis model. Systemic or topical ISS after RW sensitization inhibits both immediate hypersensitivity response and the late-phase cellular infiltration and induced a RW-specific Th1 response. ISS may provide an alternative to the current standard care of ocular allergy.