Photoreceptor Differentiation following Transplantation of Allogeneic Retinal Progenitor Cells to the Dystrophic Rhodopsin Pro347Leu Transgenic Pig
We have shown previously that fetal retinae transplanted to neonatal rat brains are capable of making the pretectal connections necessary for driving a pupillary reflex in response to light. At birth, the rat brain is still developing and presents a favorable environment for fiber outgrowth and synaptogenesis. A remaining question is whether such grafts will also establish functional connections within the less plastic mature brain. Fetal retinae taken from Sprague-Dawley rats at embryonic day 13 or 14 were implanted in the pretectal region of mature host rats ranging in age from 6 to 11 weeks. The contralateral host eye was removed to reduce afferent competition within the pretectum between the optic input of graft and host. The remaining host optic nerve was cut before testing to eliminate all remaining host visual input. Beginning 1 month after transplantation, the retinae were surgically exposed and illuminated. In 6 of 24 animals, illumination elicited an obvious pupilloconstriction response in the host eye. The magnitude of this graft-mediated response varied between animals. Two animals produced very brisk responses, comparable to the best results seen following transplantation into neonatal hosts. In these cases, the degree of constriction was clearly dependent on the level of graft illumination. The 4 other animals produced responses that were less brisk. All 6 animals with clear-cut graft-mediated pupillary responses had well-formed grafts containing numerous rosettes and ganglion cells. In addition to these 6 animals, 9 others showed extremely small or variable pupillary changes on graft illumination. The remaining 9 animals showed no stimulus-associated pupillary activity. Grafts in this group tended to be poorly formed or were located outside the pretectal area. These results show that transplanted retinae are capable of making specific functional connections with the mature brain, since an appropriate visual reflex can be elicited by illuminating the graft in the absence of host visual input.