IMMUNOPATHOLOGY IN EYES WITH EXPERIMENTAL AND CLINICAL OCULAR DISEASES

采用免疫组织化学、原位杂交、聚合酶链反应（PCR）和显微解剖等方法分析患者样本和各种实验性葡萄膜炎动物模型中细胞及其标志物的身份和地形定位。在1999财年，我们完成了以下4个研究课题：1。原发性眼内淋巴瘤细胞的基因和蛋白检测。利用显微解剖和PCR技术，我们将一些感染因子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细胞淋巴瘤与玻璃体内IL-10水平和IL-10:IL-6比值之间的关系，这可以提高这种肿瘤的诊出率。HTLV-1感染与T细胞白血病/淋巴瘤。利用显微解剖和PCR技术，我们研究并证实了HTLV-1病毒基因和T细胞受体基因重排在HTLV-1相关的T细胞白血病/淋巴瘤中。3. 内毒素诱发葡萄膜炎（EIU）的发病机制采用ELISA和RT-PCR技术，研究了细胞因子在小鼠EIU中的动力学和病理变化。我们发现这种疾病与眼部各种细胞因子水平密切相关，尤其是IL-6。在最敏感的菌株C3H/HeN中，对LPS的眼部炎症反应是双期的。相比之下，眼部炎症是单相的，没有两个细胞因子波。4. 变应性结膜炎的调节。我们发现免疫刺激DNA序列（ISS）可以抑制豚草（RW）诱导的小鼠变应性结膜炎模型中正在进行的Th2/过敏反应，并诱导重新产生Th1反应。RW致敏后的全身或局部ISS可抑制即时超敏反应和晚期细胞浸润，并诱导RW特异性Th1反应。ISS可能为目前眼部过敏的标准治疗提供了另一种选择。

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.