Primary Intraocular Lymphoma and Animal Models

目前尚无已知的潜在遗传缺陷导致患者发生原发性眼内淋巴瘤(PIOL)。发现易发生PIOL的遗传因素将有助于PIOL的早期诊断、预后分期和新的治疗方法的开发。白介素10和白介素6在PIOL患者的玻璃体体液和脊髓液中的比例失调，这导致了一种假说，即这些或其他白介素类的功能或表达的改变可能导致这种罕见的疾病的发生。 恶毒。我们研究了使用CD-22/假单胞菌来杀灭眼内肿瘤。人类原发性眼内淋巴瘤(PIOL)是一种主要来源于B细胞的恶性疾病，目前尚无合适的动物模型和有效的治疗方法。本研究旨在建立一种接近模拟人类B细胞PIOL的小鼠模型，并测试最近开发的一种针对人类B细胞淋巴瘤的免疫毒素的治疗潜力。将人B细胞淋巴瘤细胞注射入严重联合免疫缺陷小鼠的玻璃体内，通过眼底镜、组织病理学、免疫组织化学和分子标志物评价该肿瘤模型与人PIOL的相似性。玻璃体腔内注射免疫毒素HA22检测其治疗效果。结果表明，所建立的小鼠模型与人PIOL非常相似。病理检查显示，肿瘤细胞最初定植于视网膜表面，随后渗入视网膜各层，优先在视网膜下间隙扩张，最终穿透视网膜色素上皮进入脉络膜。肿瘤转移到中枢神经系统也被观察到。在PIOL建立后，一次玻璃体内注射免疫毒素HA22导致肿瘤完全消退。这是首次报道了一种非常接近于人类B细胞Piol的小鼠模型。B细胞特异性免疫毒素治疗的结果可能对人PIOL的治疗有临床意义。我们希望开发新的方法，利用临床上可用的技术，如OCT，在人眼中显示肿瘤。长期计划是进行I/II期试验，以评估这种免疫毒素作为PIOL的替代局部治疗方法。

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. 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. We investigated the use of a CD-22/pseudomonas construct in order to kill intraocular tumor. Human primary intraocular lymphoma (PIOL) is predominantly a B celloriginated malignant disease with no appropriate animal models and effective therapies available. This study aimed to establish a mouse model to closely mimic human B-cell PIOL and to test the therapeutic potential of a recently developed immunotoxin targeting human B-cell lymphomas. Human B-cell lymphoma cells were intravitreally injected into severe combined immunodeficient mice.The resemblance of this tumor model to human PIOL was examined by fundoscopy, histopathology, immunohistochemistry, and evaluated for molecular markers. The therapeutic effectiveness of immunotoxin HA22 was tested by injecting the drug intravitreally. Results showed that the murine model resembles human PIOL closely. Pathologic examination revealed that the tumor cells initially colonized on the retinal surface, followed by infiltrating through the retinal layers, expanding preferentially in the subretinal space, and eventually penetrating through the retinal pigment epithelium into the choroid. Tumor metastasis into the central nervous system was also observed. A single intravitreal injection of immunotoxin HA22 after the establishment of the PIOL resulted in complete regression of the tumor. This is the first report of a murine model that closely mimics human B-cell PIOL. The results of B cellspecific immunotoxin therapy may have clinical implications in treating human PIOL. We are hoping to develop new methods to visualize the tumor in the human eye using techniques available in the clinic, such as OCT. The long term plan is to do a phase I/II trials to evaluate this immunotoxin as an alternative, localized therapy for PIOL.