M. Delcerro et al., TRANSPLANTATION OF Y79 CELLS INTO RAT EYES - AN IN-VIVO MODEL OF HUMAN RETINOBLASTOMAS, Investigative ophthalmology & visual science, 34(12), 1993, pp. 3336-3346
Purpose. To develop an in vivo model of human retinoblastoma by return
ing 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. Methods. Using the retinal grafting
method of Lazar and del Cerro, Y79 cells were injected under direct v
isualization into the subretinal space of Fischer 344 rats. The host r
ats included 36 animals that received daily injections of cyclosporin
A and 4 that did not. All hosts were sacrificed 30 to 60 days after tr
ansplantation. Results. Clinical examination showed vitreal invasion b
y masses of flocculent white material or the intravitreal formation of
solid tumors. Histologic examination showed these formations to be ou
tgrowths of grafted tumoral cells into the host retina and vitreal cav
ity. Highly anaplastic tumoral cells were also found lodged in subreti
nal and intraretinal locations. There were signs of continued and inte
nse cell division within the grafts, with no indication of cell-mediat
ed host reaction against the grafted cells. Conclusions. After intrare
tinal xenografting, human Y79 retinoblastoma cells retain a highly tum
oral nature despite many years of in vitro propagation. When xenograft
ed, these cells survive, grow, and express their malignancy within the
retina of the common laboratory rat protected by a moderate immunosup
pressive 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 hu
man retinoblastomas, and it may facilitate the evaluation of antitumor
al treatments.