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）、显微解剖和图像分析，分析患者标本中浸润细胞（如炎症细胞和肿瘤细胞及其产物）的身份和地形定位。利用这些技术，我们将从所研究的组织中对疾病进行准确的病理评估，指导患者进行适当的治疗，并了解疾病的发病机制。在2001财年，我们继续并完成了以下研究：原发性眼内淋巴瘤细胞的基因和蛋白检测。我们利用显微解剖和PCR技术继续检测IgH基因重排，并在有临床表现但细胞学检查不佳的病例中诊断b细胞淋巴瘤。我们在原发性眼内淋巴瘤中检测到包括刚地弓形虫在内的几种感染因子的DNA存在，但在眼睛中没有正常细胞。我们推测感染因子可能在某些形式的原发性眼内淋巴瘤中起作用。此外，我们还说明了原发性眼内淋巴瘤的荧光素血管造影结果。2. 眼部炎症及其他疾病的新病理及发病机制。我们在HTLV-1感染引起的视网膜血管炎浸润细胞中检测t细胞受体基因重排和HTLV-1基因。我们报告了由人乳头瘤病毒33型引起的结膜乳头瘤。我们首次在神经纤维瘤病患者的视网膜和视神经病变中证实NF2基因的杂合性缺失2。我们报道了IV型粘脂病的无创诊断和眼科特征。各种非炎性眼病的实验模型。我们研究了趋化因子在眼部炎症中的作用。通过内毒素诱导的葡萄膜炎模型（EIU），我们发现MCP-1在EIU发生中的重要作用。我们还发现细胞凋亡和γ干扰素在小鼠弓形虫病中的作用。与NEI以外的研究人员合作，我们证明了雌激素受体抑制因子诱导白内障形成（与D.L. Davis合作）。在hiv转基因小鼠中观察到先天性核性白内障和轻度葡萄膜炎（与J.B. Kopp）。这些发现表明，眼部病理是各种全身性疾病的重要表现。

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 contiuned to detect IgH gene rearrangemnts and diagnose B-cell lymphoma in those cases of clinical manifestions but poor cytology. 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 infectious agents might play a role in some forms of primary intraocular lymphoma. In addition, we illustrated fluorescein angiographic findings in primary intraocular lymphoma. 2. New Pathology and Pathogenesis of Ocular Inflammation and Other Diseases. We detected T-cell receptor gene rearrangement and HTLV-1 gene in the infiltrating cells of retinal vasculitis caused by HTLV-1 infection. We reported conjunctival papillomas caused by human papilloma virus type 33. We demonstrated first time the loss of heterozygosity for the NF2 gene in retinal and optic nerve lesions of patients with neurofibromatosis 2. We reported noninvasive diagnosis and ophthalmic features of mucolipidosis type IV. 3. Experimental Models for Various Non-Inflammatory Ocular Diseases. We studied the role of chemokines in ocular inflammation. Using endotoxin-induced uveitis model (EIU), we showed the importance of MCP-1 in initiation of EIU. We also showed the involvement of apoptosis and gamma interferon in murine toxoplasmosis. In collaboration with investigators outside the NEI, we demonstrated that estrogen receptor repressor induced cataract formation (with D.L. Davis). Congenital nuclear cataracts and mild uveitis are observed in HIV-transgenic mice (with J.B. Kopp). These findings demonstrate that ocular pathology is an important manifestation of various systemic diseases.