TRANSPLANTATION OF HUMAN FETAL RETINAL-PIGMENT EPITHELIUM RESCUES PHOTORECEPTOR CELLS FROM DEGENERATION IN THE ROYAL-COLLEGE OF SURGEONS RAT RETINA

Purpose. The Royal College of Surgeons (RCS) rat suffers from a well-c haracterized, early-onset, and relentless form of photoreceptor cell d egeneration. It has been shown that allografts of retinal pigment epit helial cells from normal perinatal rats have rescue effects in this co ndition. In preparation for human application, the authors determined whether human fetal retinal pigment epithelium (RPE) grafts have a pho toreceptor rescue effect in RCS dystrophic rat retinas. Methods. Sheet s of RPE from human fetal eyes (10 to 16 weeks gestational age) were i solated according to the authors' recently described method. Fragments of the RPE sheets were transplanted to the subretinal space within th e superior hemisphere. Transplants were performed within the superior equatorial region of five dystrophic RCS rats, one eye per animal. A s imilar volume of vehicle was injected into the subretinal space of fiv e age-matched control rats, again one eye-per rat. All mts were immuno suppressed with daily injections of cyclosporine. Using light microsco py, photoreceptor cell nuclear profiles of superior equatorial (SE) an d inferior equatorial (IE) regions of transplanted and sham-injected c ontrol animals were counted. Results. Four weeks after transplantation , a dramatic rescue effect was observed. Microscopically, presumptive donor RPE cells were seen as single pigmented cells and as cell duster s in the subretinal space. An outer nuclear layer three to four profil es 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 mu m was 3 4.7 +/- 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 eviden ce of graft rejection was seen. Conclusions. This study provides the f irst indication that transplanted human fetal RPE cells are able to re scue photoreceptor cells in a model of hereditary retinal degeneration .