Primary Intraocular Lymphoma and Animal Models

没有已知的潜在遗传缺陷诱发患者 原发性眼内淋巴瘤（PIOL）。发现遗传 诱发PIOL发展的因素将有利于 早期诊断、预后分期和开发新的治疗方法 对于PIOL。直到最近，研究病因学的遗传学方法 依赖于利用基于传统 孟德尔遗传模式。许多疾病可能是一种 多种遗传因素的结果，因此不太容易接受 使用传统的连锁分析和定位方法进行研究， 克隆以分离单个基因。单核苷酸多态性 是人类基因组中最常见的变异来源。snp是 在DNA序列中可以观察到的单碱基差异， 一个人口中的个体。SNP是基于频率定义的。 在一个或多个人群中至少有1%的患病率。snp存在 在整个基因组中以1/1000碱基对的平均频率。我们 我建议分析编码中SNP的频率， 生物学上合理的基因框架负责的功能， 先天免疫系统白细胞介素是一种特殊的途径 因为之前的研究已经表明， 患者玻璃体液和脊髓液中的白细胞介素10和6 与PIOL，导致的假设，改变功能或表达 这些或其他白细胞介素可以允许这种罕见的发展， 恶性肿瘤继续收集样本，但由于尚未有结果， 得出了我们过去在NIH举办了一个关于这个主题的研讨会 财政年度，最近公布的结果。自从招募 这项研究进展非常缓慢，我们决定暂停这项研究。 然而，我们收到了一个从板凳到床边的奖项，开始调查使用一个 CD-22/假单胞菌构建体以杀死眼内肿瘤。初始 我们计划在动物身上进一步开展这些研究， 研究和最终治疗患者。 从2005年到2007年，我们在建立 小鼠模型来模拟人PIOL以及寻找新的和 有效治疗这种疾病。我们建立了一个小鼠模型， 在组织病理学和分子水平上类似于人PIOL 发病机制我们证明了模型共享几个霍尔标记， 人PIOL的特性，是进一步研究PIOL的理想选择。 人PIOL的分子机制。此外，在与 NCI，我们发现最近开发的免疫毒素（HA 22）可以根除 肿瘤具有最小的毒性，是一种潜在的新的治疗方法， 用于治疗人PIOL的药剂。目前，我们正在研究HA 22的毒性。 眼组织中的一种。

There is no known underlying genetic defect predisposing patients to develop primary intraocular lymphoma (PIOL). Discovery of genetic factors predisposing to the development of PIOL would be of benefit for early diagnosis, prognostic staging, and development of novel treatments for PIOL. Until recently, genetic approaches to investigate the etiology of cancer have relied upon methods utilizing linkage based on traditional Mendelian inheritance patterns. It is probable that many diseases are a consequence of multiple genetic factors, and are therefore less amenable to study using traditional methods of linkage analysis and positional cloning to isolate single genes. Single nucleotide polymorphisms (SNPs) are the most common sources of variation in the human genome. SNPs are single-base differences in the DNA sequence that can be observed among individuals in a population. A SNP is defined on the basis of a frequency of at least 1% prevalence in one or more populations. SNPs are present throughout the genome at an average frequency of 1/1000 base pairs. We propose to analyze the frequency of SNPs specifically within the coding frames of biologically plausible genes responsible for function of the innate immune system. The interleukins are a specific pathway of interest because previous research has demonstrated derangements in the ratios of interleukins 10 and 6 in the vitreous humor and spinal fluid of patients with PIOL, leading to the hypothesis that altered function or expression of these or other interleukins could permit the development of this rare malignancy. Samples continue to be collected, but as no results have yet been obtained. We hosted a workshop on this subject at the NIH this past fiscal year with the results recently published. Since recruitment for this study was very slow we have made the decision to suspend this study. However, we received a Bench to Bedside award to begin to investigate the use of a CD-22/pseudomonas construct in order to kill intraocular tumor. Initial studies have been promising with our plan to carry these further in animal studies and ultimately to the treatment of patients. From 2005 to 2007, we have made substantial progress in establishing a murine model to mimic human PIOL as well as searching for novel and effective therapy for this disease. We have established a mouse model that resembles human PIOL at the level of histopathology and molecular pathogenesis. We demonstrated that the model shares several hall mark characteristics of human PIOL and is ideal for further studying the molecular mechanisms of human PIOL. Furthermore, in collaboration with NCI, we found that a recently developed immunotoxin (HA22) can eradicate the tumor with minimal toxicity and is potentially a novel therapeutic agent for treating human PIOL. Currently, we are investigating the toxicity of HA22 to ocular tissues using a rabbit model.