Primary Intraocular Lymphoma and Animal Models

National Eye Institute

Investigators

Linked publications & trials

Abstract

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