Primary Intraocular Lymphoma and Animal Models

没有已知的潜在遗传缺陷使患者易患原发性眼内淋巴瘤（PIOL）。发现易患PIOL的遗传因素将有利于PIOL的早期诊断、预后分期和开发新的治疗方法。 白细胞介素是感兴趣的特定途径，因为先前的研究已经证明PIOL患者的玻璃体液和脊髓液中白细胞介素10和6的比例紊乱，导致假设这些或其他白细胞介素的功能或表达改变可以允许这种罕见的疾病的发展。 恶性肿瘤我们研究了CD-22/假单胞菌构建体的使用以杀死眼内肿瘤。 人原发性眼内淋巴瘤（PIOL）是一种主要起源于B细胞的恶性肿瘤，目前尚无合适的动物模型和有效的治疗方法。本研究的目的是建立一个小鼠模型，以密切模拟人类B细胞PIOL和测试最近开发的免疫毒素靶向人类B细胞淋巴瘤的治疗潜力。将人B细胞淋巴瘤细胞玻璃体腔内注射到严重联合免疫缺陷小鼠体内，通过眼底镜、组织病理学、免疫组化和分子标记物的检测，观察该肿瘤模型与人PIOL的相似性。通过玻璃体内注射免疫毒素HA_（22）检测其治疗效果。结果表明，小鼠模型与人PIOL非常相似。病理学检查显示肿瘤细胞最初在视网膜表面定植，随后浸润穿过视网膜层，优先在视网膜下腔扩展，并最终穿透视网膜色素上皮进入脉络膜。还观察到肿瘤转移到中枢神经系统。单次玻璃体内注射免疫毒素HA 22后，建立的PIOL导致肿瘤完全消退。这是第一次报告的小鼠模型，密切模仿人类B细胞PIOL。B细胞特异性免疫毒素治疗的结果可能对治疗人PIOL具有临床意义。我们希望开发新的方法来可视化肿瘤在人眼中使用的技术在临床上，如OCT。长期计划是做一个I/II期试验，以评估这种免疫毒素作为一种替代，局部治疗PIOL。

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.