Efficacy of nonfetal human RPE for photoreceptor rescue: a study in dystrophic RCS rats.
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 degrees 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.
Castillo
B V
BV
Department of Neurobiology and Anatomy, University of Rochester Medical Center, New York 14642, USA.
del Cerro
M
M
White
R M
RM
Cox
C
C
Wyatt
J
J
Nadiga
G
G
del Cerro
C
C
D000368:Aged; D000704:Analysis of Variance; D000818:Animals; D002470:Cell Survival; D017690:Cell Transplantation; D002648:Child; D016572:Cyclosporine / Q000627:therapeutic use; D006801:Humans; D007165:Immunosuppression Therapy; D009137:Muscular Dystrophy, Animal / Q000473:pathology*; D010786:Photoreceptor Cells / Q000473:pathology*; D010857:Pigment Epithelium of Eye / Q000637:transplantation*; D051381:Rats; D011922:Rats, Mutant Strains; D012162:Retinal Degeneration / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D014183:Transplantation, Heterologous
D016572:Cyclosporine