Because a major cause of blindness is the destruction of the retinal photoreceptors work was initiated in this laboratory to investigate the possibility of restoring some level of visual function through the transplantation of photoreceptors. To this end, a method for separating the intact photoreceptor matrix from the developing retina has been devised, and we have found that with careful surgery, transplantation of these photoreceptors to their appropriate position behind the retina is possible. It is advantageous that the neural connections which the photoreceptors must make to the neural retina are short and that the photoreceptors need to appropriately innervate only the adjacent outer plexiform layer in order for photic activation to be restored. In addition, because transplant tissue rejection is minimal within the eye and since nonvascularized tissue within the eye has shown the least amount of tissue rejection, the chance of the nonvascularized photoreceptor tissue being rejected is limited. This limited vulnerability to transplant rejection in the photoreceptor layer opens up the possibility for the transplantation of tissue that is genetically dissimilar, which would have considerable clinical utility. Adult albino rats were blinded by two to four weeks of constant illumination which destroyed the photoreceptors and left the remaining neural retina intact. Photoreceptors for transplantation were taken from neonatal rats of the same strain. In order to maintain the organization of the photoreceptor layer, we devised a method for separating the intact photoreceptor matrix, the outer nuclear layer, from the immature retina. Transplantation of the photoreceptor matrix to the host's retina was accomplished using a transcorneal approach to the subretinal space, which minimized vascular trauma to the eye. We found that this approach does not appear to disrupt the integrity of the retina which spontaneously reattaches to the back of the eye with the transplanted photoreceptors interposed between the retina and the underlying tissues. The photoreceptors survive transplantation, showing appropriate growth and development as well as physical integration with the blinded host's retina. These findings indicate that retinal photoreceptors can be successfully transplanted to form a new outer nuclear layer with mature blind retina. Metabolic tracing and electrophysiological measures indicate that some degree of visual transduction has been restored to the blinded retina by the transplanted photoreceptors. Further experiments are planned to maximize and test for the survival and appropriate development as well as anatomical and functional integration of the transplanted photoreceptors with the host's blinded retina.
| Silverman, M S; Hughes, S E; Valentino, T L et al. (1992) Photoreceptor transplantation: anatomic, electrophysiologic, and behavioral evidence for the functional reconstruction of retinas lacking photoreceptors. Exp Neurol 115:87-94 |
| Silverman, M S; Hughes, S E (1990) Photoreceptor rescue in the RCS rat without pigment epithelium transplantation. Curr Eye Res 9:183-91 |
| Silverman, M S; Hughes, S E (1989) Transplantation of photoreceptors to light-damaged retina. Invest Ophthalmol Vis Sci 30:1684-90 |
