The use of retinal transplantation as a possible therapy for retinal degenerative diseases appears to be progressing rapidly to the human study stage. This chapter discusses number of findings critical to the progress of this field. The current retinal transplantation work encompasses a number of different strands of research that have developed independently, as well as with reference to each other, and have recently begun to integrate. The broad areas of research are sub-retinal transplants, which initially focused on reconstruction of retinal structure, but have subsequently examined functional recovery; and peripheral nerve grafts, which have studied the ability of inner retinal cells—specifically retinal ganglion cell—to regenerate functional connections with central visual structures. However, a limitation to grafting as a routine therapy lies in sourcing of cells. Freshly harvested cells present logistic problems, not only in supply of suitable donor retinae, but also in screening the cells sufficiently for infective agents.

Anosova, Natalie G.1; Boisgerault, Florence1; Fedoseyeva, Eugenia V.1; Whiteley, Simon1; Illigens, Ben1; Young, Michael1; Benichou, Gilles1 Author Information

The functional reinnervation of the olivary pretectal nucleus (OPN) was studied in adult rats with peripheral nerve (PN) grafts bridging the interrupted retinopretectal pathway. Functional recovery was assessed quantitatively using established pupillometry techniques. The effect of intravitreal tuftsin fragment 1-3 (tuftsin 1-3) injections during the grafting procedure was also studied. A total of 53 adult rats received autologous PN grafts connecting the ocular stump of the transected optic nerve to the ipsilateral OPN. The contralateral eye was enucleated to remove the input from that eye to the OPN. A pupillary light reflex was elicited from 35 of the 53 PN-grafted animals and in the best cases, a response was obtained which compared closely to that recorded from control animals. Tuftsin 1-3 was found to increase the rate of recovery of the response. The response amplitude of PN-grafted rats was generally found to diminish with repeated stimulus presentation and also appeared to deteriorate with age. This was in contrast to control animals' responses. However, a PLR could still be elicited in 3 of the 6 animals studied 15 months after PN-grafting. These findings indicate that a near-normal PLR function can be restored using a peripheral nerve graft, but there are a number of factors that are likely to compromise optimal outcome.

The Royal College of Surgeons rat provides a valuable animal model for examining the ontogeny of inherited or acquired photoreceptor degeneration and for assessing various treatment paradigms. Here we describe a sequence of events in which photoreceptor loss induces secondary changes that ultimately result in a progressive loss of retinal ganglion cells. The functional consequences of photoreceptor loss are described and compared with those observed in dystrophic animals that received grafts of pigment epithelial cells at an early stage in the degenerative process. The results of this work suggest that transplantation might slow or halt the progress of photoreceptor loss in certain human retinal degenerative conditions, provided suitable safeguards have been put in place.