Transplantation of Full-Thickness Retina in the Rhodopsin Transgenic Pig

Abstract

Full-thickness neuroretinal grafts can be transplanted to a large animal host with photoreceptor degeneration. The transplantation procedure is relatively atraumatic to both graft and host tissue, and the grafts survive well for at least 4 months. The graft and host retina does not seem to form extensive neuronal contacts, and future work must be directed at stimulating such activity without disrupting the retinal neuronal organization.

Long-term neuroretinal full-thickness transplants in a large animal model of severe retinitis pigmentosa

“…Additionally, most of the inner retinal layers were seen in the grafts which was somewhat surprising. We previously reported that neonatal full-thickness grafts to normal and degenerating hosts do not develop inner layers [15,16], a phenomenon best explained by the separation from its retinal blood supply [18]. The blood vessels found in all grafts in the present study, indicate that fetal full-thickness grafts can develop a new inherent retinal circulation and thereby also form inner layers.…”

“…The surgical procedures were, with a few exceptions, identical to the one reported in a previous paper [16], and will only be summarized here. Six consecutive animals were operated in 2 sessions of 3 animals each.…”

“…This phenomenon, indicating abnormal growth of the graft along the scleral-vitreal axis, has not been found in eyes transplanted with neonatal or adult donor tissue [16,31], but has been noted in short-term fetal rabbit grafts [11]. Evidently, the confined space in the subretinal space does not allow lateral expansion of the graft, which would be more desirable.…”

“…A handful of experimental studies have shown that neuroretinal transplants can survive and maintain morphologically normal photoreceptors for extended time periods if they are placed in their homotopic location in the subretinal space with correct polarity [13,16,17,29,32]. Progress has also been made in the critical area of neuronal integration between host and graft retinal neurons but this problem has not yet been adequately solved, making transmission of visual information from graft to host improbable [12,21,28].…”

“…This model, first described in 1997, involves the rhodopsin mutation Pro347Leu which in the first year of life causes severe loss of rods [25]. We previously reported transplantation of neonatal normal full-thickness neuroretina to young rhodopsin transgenic pigs, and found that such grafts survive and develop well for at least 4 months in the diseased eye [16]. However, the study did not show integration between graft and host retinal neurons since the neonatal retina kept its inherent synaptic architecture, and did not sprout new neuronal fibers towards the host.…”