Molecular And Immunopathology Of Experimental And Clinic

通过常规病理、免疫组织化学、原位杂交、显微解剖和各种分子技术，如聚合酶链式反应、逆转录聚合酶链式反应和限制性片段长度多态性分析，分析眼部炎性细胞、变性细胞和肿瘤细胞及其产物在患者标本中的特征和定位。尖端技术的应用使我们能够对疾病提供准确的病理评估，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的发病机制。在2006财年，我们继续并完成了以下研究：1.眼淋巴瘤细胞中基因和蛋白的检测：我们报道了72例原发性眼内淋巴瘤(PIOL)中56%的bcl2t(14；18)易位。尽管bcl-2t(14；18)易位与生存或复发之间没有明显的关联。易位患者明显更年轻。我们还报道了PIOL与睾丸淋巴瘤的关系。我们在结膜和眼眶MALT淋巴瘤中检测到感染基因(幽门螺杆菌或肺炎衣原体)。2.老年性黄斑变性(AMD)的分子病理学：我们检测到AMD黄斑组织中CX3CR1和ERCC6基因的单核苷酸多态频率高于正常眼，而CX3CR1和ERCC6的表达低于正常眼，证实了这两个基因与AMD的相关性研究。3.眼部疾病的新病理和发病机制：我们在与von Hippel-Lindau病相关的眼部血管母细胞瘤中发现了干细胞成分。我们报告了一例成人1型Hermansky-Pudlak综合征的眼部病理，其眼部黑素细胞稀少，主要含有III期黑素小体，很少含有IV期黑素小体。我们观察到角膜缘干细胞移植后供体上皮细胞长期存活，提示有必要进行免疫抑制治疗。我们讨论了与分枝杆菌相关的眼部炎症性疾病，以及慢性肉芽肿性疾病的眼部表现。4.多种眼部疾病的实验模型：我们在CCL2/MCP-1缺陷小鼠视网膜下注射Matrigel导致视网膜变性加重和脉络膜新生血管形成，支持炎症在AMD中的重要作用。在与Caspi、Gery和Nussenblatt博士的合作下，已经发现并发表了几种新的眼部炎症模式和机制。在与周博士的合作中，我们发现糖尿病视网膜病变患者的血清炎症标志物如ICAM-1、RANTES和CCL2升高。

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 such as 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 FY2006, we continued and accomplished the following in our research: 1. Detection of Genes and Proteins in Ocular Lymphoma Cells: We reported bcl-2 t(14;18) translocation in 56% of 72 cases with primary intraocular lymphoma (PIOL). Although there was no significant association between bcl-2 t(14;18) translocations and survival or relapse. Patients with translocation were significantly younger. We also reported a relationship between PIOL and testicular lymphoma. We detected infectious genes (H. pylori or C. peumoniae) in conjunctival and orbital MALT lymphoma. 2. Molecular pathology of age-related macular degeneration (AMD): We detected higher rates of single nucleotide polymorphisms and lower expression of CX3CR1 and ERCC6 in the AMD maculae compared to the normal eyes, which confirmed the association studies of these two genes and AMD. 3. New Pathology and Pathogenesis of Ocular Diseases: We discovered stem cell components in ocular hemangioblastomas associated with von Hippel-Lindau disease. We reported ocular pathology of Hermansky-Pudlak syndrome type 1 in an adult whose ocular melanocytes were sparse and contained mainly stage III and rarely stage IV melanosomes. We observed long term survaval of donor epithelial cells after limbal stem cell transplantation, which implied the need of immunosuppresive therapy. We discussed mycobacterium related ocular infalmmatory diseases, and ocular findings in chronic granulomatous disease. 4. Experimental Models for Various Ocular Diseases: We demonstrated exacerbation of retinal degeneration and choroidal neovascularization induced by subretinal injection of matrigel in CCL2/MCP-1 deficient mice, which supported the important role of inflammation played in AMD. In collaboration with Drs. Caspi, Gery, and Nussenblatt, several new modes and mechanisms of ocular inflammation have been discovered and published. In collaboration with Dr. Chew, we found elevated serum inflammatory markers such as ICAM-1, RANTES and CCL2 in patients with diabetic retinopathy.