del Cerro M, Seigel G M, Lazar E, Grover D, del Cerro C, Brooks D H, DiLoreto D, Chader G
Department of Neurobiology, University of Rochester School of Medicine, NY 14642.
Invest Ophthalmol Vis Sci. 1993 Nov;34(12):3336-46.
To develop an in vivo model of human retinoblastoma by returning cultured Y79 retinoblastoma cells to the retinal environment of a widely available laboratory animal. In so doing, to study the survival, integration, and invasive characteristics expressed by tumoral cells grafted into an intraocular milieu from which these progenitor cells originated more than 20 years ago.
Using the retinal grafting method of Lazar and del Cerro, Y79 cells were injected under direct visualization into the subretinal space of Fischer 344 rats. The host rats included 36 animals that received daily injections of cyclosporin A and 4 that did not. All hosts were sacrificed 30 to 60 days after transplantation.
Clinical examination showed vitreal invasion by masses of flocculent white material or the intravitreal formation of solid tumors. Histologic examination showed these formations to be outgrowths of grafted tumoral cells into the host retina and vitreal cavity. Highly anaplastic tumoral cells were also found lodged in subretinal and intraretinal locations. There were signs of continued and intense cell division within the grafts, with no indication of cell-mediated host reaction against the grafted cells.
After intraretinal xenografting, human Y79 retinoblastoma cells retain a highly tumoral nature despite many years of in vitro propagation. When xenografted, these cells survive, grow, and express their malignancy within the retina of the common laboratory rat protected by a moderate immunosuppressive regimen. This partial immunosuppression is a requirement for the xenografts to prosper. This model offers a valuable opportunity to study in vivo the cellular and molecular biology of this and other human retinoblastomas, and it may facilitate the evaluation of antitumoral treatments.
通过将培养的Y79视网膜母细胞瘤细胞放回一种广泛使用的实验动物的视网膜环境中，建立一种人视网膜母细胞瘤的体内模型。通过这样做，研究移植到眼内环境中的肿瘤细胞的存活、整合和侵袭特征，这些祖细胞在20多年前就起源于此环境。
采用拉扎尔和德尔塞罗的视网膜移植方法，在直接可视化下将Y79细胞注射到Fischer 344大鼠的视网膜下间隙。宿主大鼠包括36只每天接受环孢素A注射的动物和4只未接受注射的动物。所有宿主在移植后30至60天被处死。
临床检查显示玻璃体被絮状白色物质团块侵袭或玻璃体腔内形成实体瘤。组织学检查显示这些结构是移植的肿瘤细胞向宿主视网膜和玻璃体腔的生长。还发现高度间变的肿瘤细胞位于视网膜下和视网膜内位置。移植内有持续且强烈的细胞分裂迹象，没有细胞介导的宿主对移植细胞的反应迹象。
视网膜内异种移植后，人Y79视网膜母细胞瘤细胞尽管经过多年体外培养，仍保持高度肿瘤特性。异种移植后，这些细胞在受到适度免疫抑制方案保护的普通实验大鼠视网膜内存活、生长并表现出恶性特征。这种部分免疫抑制是异种移植成功的必要条件。该模型为体内研究这种及其他人类视网膜母细胞瘤的细胞和分子生物学提供了宝贵机会，并且可能有助于评估抗肿瘤治疗。
