Triple Immune Suppression Increases Short-Term Survival of Porcine Fetal Retinal Pigment Epithelium Xenografts

To determine the effect of triple drug immune suppression on RPE xenograft survival in the fetal pig after transplantation into the albino rabbit subretinal space. Primary RPE microaggregates (approximately 40,000 RPE cells) were injected into the subretinal space of 24 albino rabbits, with half the rabbits maintained on triple systemic immune suppression. RPE survival was estimated with a DNA probe (porcine DNA repeat element; PRE) against a porcine-specific repetitive chromosomal marker or a RAM-11 antibody against rabbit macrophages. Numerous pigmented cells were visible in the subretinal space at all time points, but most pigment-containing cells 4 weeks or more after surgery were RAM-11 positive and PRE negative. The number of PRE-positive cells in the immune-suppressed group (4193 +/- 2461, 1184 +/- 1502, and 541 +/- 324 at 4, 8, and 12 weeks, respectively) was greater than in immune-competent control animals (292 +/- 506, 193 +/- 173, and 111 +/- 96), but the difference was only statistically significant at 4 weeks. The time-dependent decrease in PRE-positive cells was more pronounced in immune-suppressed animals. Image analysis performed on serial fundus photographs and fluorescein angiograms did not detect any difference in the appearance of the grafts in immune-suppressed versus immune-competent animals. Systemic immune suppression increased the 4-week survival of porcine RPE xenografts in the albino rabbit subretinal space, but there was poor survival in immune-suppressed and -competent animals 12 weeks after surgery. Many pigment-containing cells 4 or more weeks after surgery were PRE negative, indicating that they are of host origin.