Electron microscopy of human first trimester and rat mid-term retinal cell transplants with long development time

Abstract

The ultrastructure of rat to rat and human to rat long-term transplants of retinal cell transplants has been investigated. The human transplants were examined at 30 to 41 weeks of total age after conception. Rat homotransplants were nine to ten weeks of age after conception in four cases and 20 weeks in one case. Xenotransplanted rats were immunosuppressed with Cyclosporin A.

Both xeno-and homotransplants can develop in the epiretinal or the subretinal space. The development is often heterogeneous. Photoreceptor cells can form both inner and outer segments as well as synaptic terminals. In regions corresponding to the inner plexiform layer, the adult complement of synapses has been seen, including advanced features like serial synapses as well as reciprocal synapses at bipolar cell dyads. Incompletely differentiated synapses of both amacrine and bipolar cell types have been observed, especially in rat epiretinal transplants. Ganglion cell processes have not been identified with certainty. Transplants from both species develop according to their intrinsic, genetically determined time table. Rat subretinal transplants tend to become more developed than epiretinal grafts, but only epiretinal grafts have so far been seen to make contacts with the host retina.

Connections between the transplant and the host have been seen in a number of cases, but are not a regular feature. Usually, there are no obvious specializations where transplant cells touch host photoreceptor cells or pigment epithelium. Graft cells have occasionally been found within the host retina, and nerve cell processes have been observed to cross the membrane separating epiretinal transplants and host.

Human retinal cells from first trimester embryos and rat El5 retinal cells in long-term xenotransplants are thus able to survive, differentiate, and develop synapses of normal appearance as well as complex neuronal circuits.

Key Words:

• retinal cell transplants
• ultrastructure
• homografts
• xenografts
• retinal fetal cells
• synapses