Immunopathology In Eyes With Experimental And Clinical O

通过免疫组织化学、原位杂交、聚合酶链反应（PCR）、显微切割和图像分析，分析患者标本中浸润细胞（如炎症和肿瘤细胞及其产物）的身份和地形定位。使用这些技术，我们将从所研究的组织中对疾病进行准确的病理学评估，指导对患者进行适当的治疗，并了解疾病的发病机制。 在2001财政年度，我们继续并完成了以下研究：1.原发性眼内淋巴瘤细胞基因和蛋白质的检测。利用显微切割和PCR技术，我们检测到的DNA存在的几个传染性病原体，包括弓形虫在原发性眼内淋巴瘤，但不是正常细胞的眼睛。我们推测弓形虫可能在某些形式的原发性眼内淋巴瘤中起作用。此外，我们进一步报道了B细胞淋巴瘤、玻璃体内高IL-10水平和IL-10：IL-6比值大于1之间的相关性。我们认为，这可以用来提高这种肿瘤的诊断率。2.眼部炎症及其他疾病的新病理和发病机制。我们检测了由HTLV-1感染引起的结膜T细胞淋巴瘤的T细胞受体基因重排和HTLV-1 gag基因。我们报道了相对高剂量的更昔洛韦和膦甲酸钠玻璃体腔注射治疗艾滋病患者的巨细胞病毒视网膜炎，没有视网膜毒性。除了白内障之外，在Hajdu-Cheney综合征中还发现外周视网膜改变，包括视网膜簇和变性。角膜细胞凋亡在Fuchs内皮营养不良的发病机制中起重要作用。3.各种非炎症性眼部疾病的实验模型。我们与美国国立卫生研究院的几个实验室合作，报道了胸腺素β 4促进角膜伤口愈合和抑制创伤诱导的炎症反应。结构异常，包括大脑和视网膜，视网膜发育不良，发展后的基因编码非肌肉肌球蛋白II-B重链消融。在艾滋病毒转基因小鼠中观察到先天性核性白内障和轻度葡萄膜炎。这些发现表明，眼部病理是各种系统性疾病的重要表现。

The identity and topographic localization of infiltrating cells such as inflammatory and tumor cells and their products in patient specimens are analyzed by immunohistochemistry, in situ hybridization, polymerase chain reaction (PCR), microdissection and image analysis. Using these techniques we will make an accurate pathological assessment of disease from the studied tissue, guide an appropriate treatment for the patient, and understand the pathogenesis of the disease. In FY2001 we have continued and accomplished the following research: 1. Detection of Genes and Proteins in Primary Intraocular Lymphoma Cells. Using microdissection and PCR techniques we detected the presence of DNA from several infectious agents including Toxoplasma gondii in primary intraocular lymphoma, but not normal cells in the eye. We speculated that Toxoplasma gondii might play a role in some forms of primary intraocular lymphoma. Additionally, we further reported the association between B-cell lymphoma, high intravitreal IL-10 level and IL-10:IL-6 ratio greater than 1. We suggest that this could be used to improve the diagnostic yield for this tumor. 2. New Pathology and Pathogenesis of Ocular Inflammation and Other Diseases. We detected T-cell receptor gene rearrangement and HTLV-1 gag gene in conjunctival T-cell lymphoma caused by HTLV-1 infection. We reported no retinal toxicity in relatively high dose of intravitreal ganciclovir and foscarnet treatment for cytomegalovirus retinitis in AIDS patients. In addition to cataracts, peripheral retinal changes including retinal tuft and degeneration are found in Hajdu-Cheney syndrome. Apoptosis of the corneal cells plays a role in pathogenesis of Fuchs endothelial dystrophy. 3. Experimental Models for Various Non-Inflammatory Ocular Diseases. In collaboration with several laboratories in the NIH, we reported that thymosin beta 4 promotes corneal wound healing and suppresses inflammatory response induced by trauma. Structural abnormalities including the brain and retina, retinal dysplasia, develop following ablation of the gene encoding nonmuscle myosin II-B heavy chain. Congenital nuclear cataracts and mild uveitis are observed in HIV-transgenic mice. These findings demonstrate that ocular pathology is an important manifestation of various systemic diseases.