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。应用显微切割和PCR技术，对临床表现明显而细胞学检查不佳的B细胞淋巴瘤进行IgH基因检测和诊断。我们在原发性眼内淋巴瘤中检测到包括弓形虫在内的几种感染因子的DNA，但在眼内正常细胞中没有检测到。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，我们举例说明荧光素血管造影的结果在原发性眼内淋巴瘤。2.眼部炎症及其他疾病的新病理和发病机制。我们检测了HTLV-1感染引起的视网膜血管炎的浸润细胞中T细胞受体基因重排和HTLV-1基因。我们报告结膜乳头状瘤引起的人乳头状瘤病毒33型。我们首次证实了NF 2基因在神经纤维瘤病2型患者视网膜和视神经病变中的杂合性缺失。我们报告了IV型粘脂沉积症的非侵入性诊断和眼科特征。3.各种非炎症性眼部疾病的实验模型。我们研究了趋化因子在眼部炎症中的作用。利用内毒素诱导的葡萄膜炎模型（EIU），我们显示了MCP-1在EIU启动中的重要性。我们还表明，在小鼠弓形虫病的细胞凋亡和γ干扰素的参与。与NEI以外的研究者合作，我们证明了雌激素受体抑制剂诱导白内障形成（D.L. Davis）。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（J.B. Kopp）。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 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.