CO-TRANSPLANTATION OF EMBRYONIC RETINA AND RETINAL-PIGMENT EPITHELIAL-CELLS TO RABBIT RETINA

The retinal pigment epithelium (RPE) is important for normal developme nt of the neural retina. We sought to investigate whether cografting R PE cells affected the differentiation and survival of retinal grafts. Pigmented embryonic day 16 (E16) rabbit retina was dissected either wi th or without attached RPE and injected into a lesion site in retinas of young adult rabbit hosts. Each host obtained a pure retina graft in one eye and a retina/RPE cograft in the other. Animals were sacrifice d after 4, 8 and 12 weeks. After 4 weeks, grafts (1-2 mm in diameter) were seen in both experimental groups at the lesion site or in the sub retinal space. However, 8 and 12 weeks after transplantation, tb: graf t survival rate decreased, The grafts developed cell layers in folded sheets and many rosettes (a rosette consists of photoreceptors and cel ls of other retinal layers around a central lumen defined by an outer limiting membrane). Cografts of retina with RPE had areas of more dist inct cell lamination than transplants of pure retina. Grafted RPE cell s were organized in clusters of cells surrounded by extracellular matr ix and often associated with blood vessels. If the extracellular matri x of RPE cell clusters was outside the rosettes close to inner retinal layers in the graft, transplant Muller cell endfeet developed an inne r limiting membrane. Muller cell endfeet could also be observed in sub retinal transplants attached to the denuded Bruch's membrane of the ho st. In 12-week grafts, when RPE cell clusters were inside rosettes, th e surrounded photoreceptors survived better. No RPE effect could be se en if single RPE cells were dispersed among retinal donor cells. In gr afts with retina alone, no inner limiting membrane was seen, and most photoreceptors were degenerated at 12 weeks. In summary, cografting of rabbit embryonic RPE cells and retina apparently induces the formatio n of an inner limiting membrane that is not seen in rabbit grafts of r etina alone. In addition, cografted RPE cells can promote the long-ter m survival of transplant photoreceptors.