HUMAN EMBRYONIC RETINAL CELL TRANSPLANTS IN ATHYMIC IMMUNODEFICIENT RAT HOSTS

This study investigates the possibility to use the athymic ''nude'' ra t as a host for the transplantation of human embryonic retinal cells w ithout immunosuppression. The long-term development of such transplant s is compared with results from our earlier study that used immunosupp ressed rats, and showed transplant immunoreactivity for S-antigen. Sev eral additional cell markers have been included: rhodopsin, rod (alpha -transducin, neuron-specific enolase (NSE), synaptophysin (SYN), cone- specific opsins, vimentin, cellular retinaldehyde binding protein (CRA LBP), glial fibrillary acidic protein (GFAP), rat major histocompatibi lity antigen class II (MHC-II) and a rat macrophage marker (Ox-42). Hu man retinal cells (9-13 wk postconception) were transplanted to the ey es of 28 athymic rats. Host rats mere kept in microisolator cages for up to 48 wk after surgery. Host immune response and the development of the transplants mere studied using histology, immunohistochemistry an d electron microscopy. When using retinas of donors 9-11 wk postconcep tion, transplants grew to 2-3 mm in diameter with many rosettes, in 31 of 35 eyes. Transplants derived from donors 12-13 wk postconception d id not survive as well (8 out of 11 eyes), were smaller and less organ ized. All transplants fused well with the host retina, better than cor responding transplants to immunosuppressed rat hosts. Most transplants appeared to be healthy, even after long survival times, and only occa sionally were MHC-II positive macrophages observed in transplants or h ost retinas. All retinal layers were observed, except for an inner lim iting membrane on the vitreous surface. The oldest transplants (34-57 wk total age = donor age + time after surgery) exhibited well develope d photoreceptors, rods and cones, with inner and outer segments. SYN-s taining showed the development of inner and outer plexiform layers. Al though many cones stained for SYN and NSE, few were immunoreactive for red-green or blue opsin. Most rods became immunoreactive for S-antige n and rhodopsin. Transplant Muller cells stained for vimentin and CRAL BP. Immunoreactivity for GFAP developed slowly and was not completely expressed in all transplant Muller cells until 44 wk total age. Nude r ats offer an excellent model for the study of human retinal xenografts without the negative effects of immunosuppression. Compared to immuno suppressed rats, transplantation to nude rats gives consistent results and superior long-term survival of hosts and transplants.