Immunopathology Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-1857, USA.
Histol Histopathol. 2012 Aug;27(8):975-84. doi: 10.14670/HH-27.975.
Von Hippel-Lindau (VHL) disease is a highly penetrant autosomal dominant systemic malignancy that gives rise to cystic and highly vascularized tumors in a constellation of organs. Patients with VHL disease commonly present with hemangioblastomas in the central nervous system and the eye while other manifestations include pheochromocytoma, clear cell renal cell carcinoma, endolymphatic sac tumors of the middle ear, pancreatic cystadenomas, epididymal and broad ligament cystadenomas. Animal models inactivating the VHL gene product in various organ tissues have been constructed over the past 15 years to parse its HIF-associated mechanisms and its link to tumorigenesis. These models, despite advancing our understanding the molecular role of VHL, are by and large unable to recapitulate the more common features of human VHL disease. Up to date, no model exists that develop retinal hemangioblastomas, the most common clinical manifestation. The purpose of this review is: (1) to discuss the need for an ocular VHL model, (2) to review the animal models that recapitulate clinical VHL disease and (3) to propose potential mechanisms of tumorigenesis for the development of ocular VHL.
希佩尔-林道（VHL）病是一种高外显率的常染色体显性遗传系统性恶性肿瘤，在一系列器官中产生囊性和高度血管化的肿瘤。患有 VHL 病的患者通常在中枢神经系统和眼睛中出现血管母细胞瘤，而其他表现包括嗜铬细胞瘤、肾透明细胞癌、中耳内淋巴囊肿瘤、胰腺囊腺瘤、附睾和阔韧带囊腺瘤。在过去的 15 年中，为了分析其与 HIF 相关的机制及其与肿瘤发生的联系，构建了在各种组织器官中失活 VHL 基因产物的动物模型。尽管这些模型提高了我们对 VHL 分子作用的认识，但它们在很大程度上无法再现人类 VHL 病的更常见特征。迄今为止，还没有建立能够发展出视网膜血管母细胞瘤（最常见的临床表现）的模型。本文综述的目的是：（1）讨论建立眼部 VHL 模型的必要性，（2）综述再现临床 VHL 病的动物模型，（3）提出眼部 VHL 发生的肿瘤发生潜在机制。
