Molecular And Immunopathology Of Ocular Diseases

通过常规病理学、免疫组织化学、原位杂交、显微切割和各种分子技术（包括PCR、RT-PCR和RFLP分析）分析患者标本中眼部炎症、变性和肿瘤细胞及其产物的身份和地形位置。尖端技术的应用使我们能够对疾病进行准确的病理评估，指导我们为患者选择合适的治疗方法，并帮助我们更好地了解疾病机制。在2005财政年度，我们继续并完成了以下研究：1.眼淋巴瘤细胞基因和蛋白质的检测：我们继续检测IgH基因重排和玻璃体IL-10升高作为原发性眼内B细胞淋巴瘤（PIOL）诊断的有用指标。另有7例新病例被诊断为PIOL。2.眼部炎症和其他疾病的新病理学和发病机制：我们报道了妊娠期葡萄膜炎活动减少。我们研究了33个艾滋病尸检眼更昔洛韦植入的病理学，发现他们在眼睛内耐受良好。利用显微切割和分子分析，我们是第一组检测到幽门螺杆菌（H。pylori）DNA在结膜粘膜相关淋巴组织（MALT）淋巴瘤中的表达。我们还确定了在视神经血管母细胞瘤的空泡化“基质”细胞中的von Hippel-Lindau（VHL）基因的杂合性缺失，并证明了VHL细胞中低氧诱导因子（HIF）和泛素的高表达。3.各种炎症和其他眼部疾病的实验模型：我们开发了一种新的原发性眼内淋巴瘤小鼠模型。我们报道了一种新的小鼠模型，眼表疾病，并导致失明与X连锁无汗性外胚层发育不良破坏。我们继续研究炎症介质和细胞因子在内毒素诱导的葡萄膜炎（EIU）模型中的作用，EIU模型是一种人类前葡萄膜炎模型。我们报道了环氧合酶-2（COX 2）缺陷小鼠的EIU增强，其中干扰素-γ可以适度逆转这种恶化并防止EIU。与Caspi、Gery和Nussenblatt博士合作，发现并发表了几种新的眼部炎症模式和机制。

The identity and topographic location of ocular inflammatory, degenerative, and tumor cells and their products in patient specimens are analyzed by routine pathology, immunohistochemistry, in situ hybridization, microdissection and various molecular techniques including PCR, RT-PCR, and RFLP assay. The application of cutting-edge technology allows us to provide accurate pathological assessments of the disease, guides us in selecting an appropriate therapy for the patient, and helps us to better understand the disease mechanisms. In FY2005, we continued and accomplished the following in our research: 1. Detection of Genes and Proteins in Ocular Lymphoma Cells: We continued to detect IgH gene rearrangements and vitreal IL-10 elevations as useful adjuncts for primary intraocular B-cell lymphoma (PIOL) diagnosis. Seven more new cases were diagnosed with PIOL. 2. New Pathology and Pathogenesis of Ocular Inflammation and Other Diseases: We reported decreasing uveitic activities during pregnancy. We studied the pathology of 33 AIDS autopsied eyes with ganciclovir implants and found that they were well tolerated within the eyes. Using microdissection and molecular analysis, we were the first group to detect Helicobacter pylori (H. pylori) DNA in the conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma. We also identified loss of heterozygosity in the von Hippel-Lindau (VHL) gene in vacuolated "stromal" cells of optic nerve hemangioblastoma and demonstrated high expression of hypoxia-inducible factor (HIF) and ubiquitin in the VHL cells. 3. Experimental Models for Various Inflammatory and Other Ocular Diseases: We developed a new murine model for primary intraocular lymphoma. We reported a novel mouse model for ocular surface disease and resultant blindness with X-linked anhidrotic ectodermal dysplasia disruption. We continued to investigate the role of inflammatory mediators and cytokines in the endotoxin-induced uveitis (EIU) model, a model for human anterior uveitis. We reported enhanced EIU in cyclooxygenase-2 (COX2) deficient mice, in which interferon-gamma could moderatedly reverse this exacerbation and protect against EIU. In collaboration with Drs. Caspi, Gery, and Nussenblatt, several new modes and mechanisms of ocular inflammation have been discovered and published.