Molecular And Immunopathology Of Experimental And Clinic

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（如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2006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检测：我们报道了72例原发性眼内淋巴瘤（PIOL）中56%存在bcl-2 t（14;18）易位。虽然bcl-2 t（14;18）易位与生存或复发之间没有显著相关性。易位患者明显年轻。我们还报道了PIOL和睾丸淋巴瘤之间的关系。我们检测了感染性基因（H. pylori或C.在结膜和眼眶MALT淋巴瘤中，2.年龄相关性黄斑变性（age-related macular degeneration，AMD）的分子病理学研究：与正常眼相比，我们检测到AMD黄斑中CX 3CR 1和ERCC 6的单核苷酸多态性发生率较高，表达较低，证实了这两个基因与AMD的相关性研究。3.眼部疾病的新病理学和发病机制：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。我们报告了一名成年人的Hermansky-Pudlak综合征1型的眼部病理学，其眼部黑素细胞稀少，主要包含III期黑素体，很少包含IV期黑素体。我们观察了角膜缘干细胞移植后供者上皮细胞的长期存活，提示免疫抑制治疗的必要性。我们讨论了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.各种眼部疾病的实验模型：我们证明了在CCL 2/MCP-1缺陷小鼠中通过视网膜下注射基质胶诱导的视网膜变性和脉络膜新生血管的恶化，这支持了炎症在AMD中发挥的重要作用。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。与Chew博士合作，我们发现糖尿病视网膜病变患者血清炎症标志物如ICAM-1，RANTES和CCL 2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.