Molecular And Immunopathology Of Ocular Diseases

通过常规病理学、免疫组织化学、原位杂交、显微解剖和各种分子技术，包括PCR、RT-PCR和RFLP测定，分析患者标本中眼部炎症细胞、退行性细胞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财年，我们继续并完成了以下工作：眼部淋巴瘤细胞中基因和蛋白的检测：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）诊断的有用辅助手段。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和发病机制：我们报道了妊娠期间葡萄膜活动减少。我们研究了33只艾滋病尸检眼植入更昔洛韦的病理，发现更昔洛韦在眼内耐受性良好。通过显微解剖和分子分析，我们是第一个在结膜粘膜相关淋巴组织（MALT）淋巴瘤中检测到幽门螺杆菌（h.p ylori） DNA的小组。我们还在视神经血管母细胞瘤的空泡“基质”细胞中发现了von Hippel-Lindau （VHL）基因的杂合性缺失，并在VHL细胞中证实了缺氧诱导因子（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：我们建立了一种新的小鼠原发性眼内淋巴瘤模型。我们报道了一种新的小鼠眼表疾病和由此导致的失明与x连锁无汗性外胚层发育不良破坏模型。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是人类前葡萄膜炎的模型。我们报道了环氧化酶-2 （COX2）缺陷小鼠的EIU增强，其中干扰素γ可以适度地逆转这种恶化并防止EIU。在与博士合作。Caspi， Gery和Nussenblatt等人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.