The Royal College of Surgeons (RCS) rat suffers from a well-characterized, early-onset, and relentless form of photoreceptor cell degeneration. It has been shown that allografts of retinal pigment epithelial cells from normal perinatal rats have rescue effects in this condition. In preparation for human application, the authors determined whether human fetal retinal pigment epithelium (RPE) grafts have a photoreceptor rescue effect in RCS dystrophic rat retinas.Sheets of RPE from human fetal eyes (10 to 16 weeks gestational age) were isolated according to the authors' recently described method. Fragments of the RPE sheets were transplanted to the subretinal space within the superior hemisphere. Transplants were performed within the superior equatorial region of five dystrophic RCS rats, one eye per animal. A similar volume of vehicle was injected into the subretinal space of five age-matched control rats, again one eye per rat. All rats were immunosuppressed with daily injections of cyclosporine. Using light microscopy, photoreceptor cell nuclear profiles of superior equatorial (SE) and inferior equatorial (IE) regions of transplanted and sham-injected control animals were counted.Four weeks after transplantation, a dramatic rescue effect was observed. Microscopically, presumptive donor RPE cells were seen as single pigmented cells and as cell clusters in the subretinal space. An outer nuclear layer three to four profiles thick was present in the area of the RPE transplant but was nearly absent in the rest of the retina, as well as in the retinas of control rats. The number of photoreceptor nuclear profiles per 100 microns was 34.7 +/- 2.2 (mean +/- SEM) in the SE region of transplanted rats and 3.5 +/- 1.4 in the same region of sham-injected rats. There were 3.0 +/- 1.0 photoreceptor nuclear profiles in the IE region of transplanted rats and 3.5 +/- 1.2 in the IE region of sham-injected eyes. No evidence of graft rejection was seen.This study provides the first indication that transplanted human fetal RPE cells are able to rescue photoreceptor cells in a model of hereditary retinal degeneration.
Editor,—Temporal artery biopsies are performed routinely on patients suspected of having giant cell arteritis. Of 131 pathology specimens examined at University of Illinois at Chicago Eye Center from 1975 to 1998, the most common diagnosis was atherosclerosis with myointimal fibrosis (63%) followed by giant cell arteritis (13%). In about 6% of cases we encountered calcific sclerosis confined to …
This study determines the efficacy of nonfetal human retinal pigment epithelium (RPE) for photoreceptor rescue utilizing the dystrophic RCS rat as an animal model. Eyes from 10- and 49-year-old donors were obtained through the Rochester Eye and Human Parts Bank. The RPE was isolated by enzymatic treatment of the choroid-RPE with 2% dispase for 30 min at 37°C. Mechanically dissociated RPE cells were injected at the superior hemisphere into the subretinal space of dystrophic RCS rats during the fourth postnatal week. Rats receiving vehicle injection served as sham controls. The animals were immunosuppressed with daily cyclosporine injections (10 mg/kg) and sacrificed 30 days posttransplantation for histologic evaluation of the RPE graft and its effect on photoreceptor survival. Transplantation of adult human RPE promoted the survival of photoreceptors in the dystrophic RCS rat. Morphometric analysis of the grafted superior hemisphere demonstrated a threefold increase in photoreceptor cell density (149.2 ± 50 SD) compared to sham controls (39.7 ± 31 SD) and the untouched inferior hemisphere (52.8 ± 28 SD). RPE from the 49-year-old donor was as effective as RPE from the 10-year-old donor in promoting photoreceptor survival. The results of this study in RCS rats suggests that RPE from adult human donors of varied ages is suitable for transplantation and retains the capability to promote survival of photoreceptor cells. This finding opens the possibility of using nonfetal RPE cells in human retinal transplantation.
