Rescue from Light-Induced Retinal Degeneration by Human Fetal Retinal Transplantation in Minipigs

Purpose: To evaluate changes in retinal morphology and visual function after transplantation of human fetal neuroretina and retinal pigment epithelium (RPE) in a minipig model of light-induced retinal degeneration. Methods: Photoreceptor degeneration was induced by 2500 lux white light exposure for six months in 16 minipigs. Human fetal (12-24 week) neuroretina and RPE were transplanted into the subretinal space adjacent to the central retina in 25 eyes. Sham operation was performed in three eyes. The operated eyes were examined by multifocal electroretinogram (mfERG), fundus fluorescence angiography (FFA), and histology for up to 12 months. Results: Subretinal transplantation of neuroretina and RPE was successful in 15 out of 25 eyes (60%), among which 10/15 eyes showed evidence of the grafted tissue in subsequent histology. Structural processes between the graft and host tissue were observed from one month post implantation, accompanied by increased numbers of GFAP-positive cells over time. Immunohistochemistry showed the presence of GFAP- and Chx10-positive cells, but rhodopsin staining was not observed within the grafted tissue. In 15 eyes, mfERG revealed retinal functional improvement in regions both inside and outside of the grafted area, but this was not observed in sham-operated eyes. FFA showed no vascular leakage or inflammatory cells in eyes receiving tissue transplants. Conclusions: Following subretinal transplantation, the grafted fetal neuroretina and RPE can survive for up to 12 months without signs of graft rejection, and the host retinas showed functional improvement over the same period. Our data suggest that subretinal transplantation of neuronal retina and RPE might be beneficial in improving retinal function in cases of retinal degeneration.