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The transplantation of different types of cells into the eye to treat retinal diseases has advanced in the past 20 years. One of the types of cells used for transplantation is the iris pigment epithelial (IPE) cell, because autologous IPE cells are easily obtained and their properties are similar to those of retinal pigment epithelial (RPE) cells and retinal cells. IPE cells are transplanted as; freshly isolated or cultured cells to replace defective or diseased RPE cells, genetically modified IPE cells for delivering target molecules to the retina or RPE, and retinal progenitor cells. IPE cells have also been transplanted for non-retinal disorders. The survival of the transplanted cells in the host is an important factor for the success of transplantation. Autologous IPE cells have been found in the transplanted subretinal space and were able to phagocytose rod outer segments even 6 months after transplantation. Allogeneic and xenogenic cells will not remain in the region longer than autologous cells. Allogenic cells transplanted into the subretinal space are rejected in humans. Thus, we have transplanted cultured autologous IPE cells in 56 patients with age-related macular degeneration. The long-term results (more than 2 years with a maximum of 8 years) showed that the visual acuity (VA) was significantly improved over the pre-transplantation VA, although a slight decrease of VA was observed 2 weeks after the transplantation. One patient showed a vasculitis-like lesion. IPE cells that were transduced with neurotrophic factors by plasmid or viral vectors have also been transplanted in animals. We have transduced several neurotrophic factor genes into IPE cells with a plasmid vector, adeno-associated virus, or adenovirus. Transplantation of these transduced IPE cells into the subretinal space rescued photoreceptor cells from several types of photoreceptor toxicities. In addition, transduction of a gene into the IPE cells suppressed the systemic dissemination of the viral genome. The neuroprotective effects of the IPE cells were different for the different types of neurotrophic factor, and some of the neurotrophic factors may enhance systemic immune reaction after transplantation. IPE cells have also been used as retinal progenital cells because they originate from the same cell lines that give rise to the neural retina and RPE cells. The transduction of the photoreceptor-related homeobox gene was reported to induce photoreceptor phenotypes in IPE cells. Furthermore, transplantations of IPE cells have been performed to treat central nervous system disorders. In this review, we summarize recent progress on IPE transplantation.

Purpose: To determine whether adenoassociated virus (AAV) vectors transduced into iris pigment epithelial (IPE) cells and transplanted into the subretinal space of rats will transfer the AAV genome to the host cells and whether the vectors are disseminated systemically., Methods: Recombinant (r)AAV was transduced into rat IPE cells and transplanted into the subretinal space of rats. For the control, rAAVs alone were injected subretinally. The transplanted IPE cells were detected by LacZ staining. Immunohistochemistry, electron microscopy, electroretinography, and fluorescein-dextran angiography were performed. DNA was extracted from various organs and blood and examined for the AAV genome by polymerase chain reaction., Results: No toxicity from rAAV transduction was observed in vitro. LacZ was expressed in the transplanted cells 1 and 2 weeks after transplantation. At 4 and 12 weeks, fewer transplanted cells were detected than at 1 week, and LacZ expression was occasionally detected at the level of host retinal pigment epithelial (RPE) cells. Expression was also detected in ciliary body epithelial cells. The electroretinograms and fluorescein-dextran angiography were only mildly altered. Significantly lower levels of AAV genome were detected in the organs and blood of rats receiving rAAV-IPE cell transplants than with direct intravenous injection of AAV vectors., Conclusions: AAV-mediated LacZ was expressed in the transplanted cells after subretinal transplantation, and the transplanted IPE cells may transfer the rAAV to host tissues, such as RPE cells, long after the transplantation. This method of gene delivery did not lead to systemic dissemination of the vectors.

Purpose: To determine whether subretinal transplantation of iris pigment epithelial (IPE) cells transduced with the adeno-associated virus (AAV2)-mediated brain-derived neurotrophic factor (BDNF) gene can protect photoreceptors against phototoxicity., Methods: The BDNF gene was inserted into AAV2 (AAV2-BDNF), and the recombinant AAV2 was transduced into rat IPE (AAV2-BDNF-IPE) cells at various multiplicities of infection (MOI). The concentrations of AAV capsids and BDNF were determined by enzyme-linked immunosorbent assay (ELISA). The AAV2-BDNF-IPE cells were transplanted into the subretinal space of rats, and the rats were placed under constant light on days 1 and 90 after the transplantation. The thickness of the outer nuclear layer was measured in histologic sections and compared to that of control sections. The expression of beta-galactosidase (LacZ) in the subretinal space was confirmed by LacZ staining after AAV2-LacZ-IPE transplantation. BDNF gene expression after transplantation was confirmed by real-time polymerase chain reaction (PCR)., Results: Transduction efficiency increased with successive days in culture and increased with higher MOI in vitro. The expression of the BDNF gene in the subretinal space was higher in AAV-BDNF-IPE than with AAV2-LacZ-IPE or with IPE-only transplantation. LacZ expression was observed in the subretinal space 7 and 90 days after transplantation. A statistically significant photoreceptor protection was observed on days 1 and 90 in eyes receiving the AAV2-BDNF-IPE transplant, in both the superior transplant site and the inferior hemispheres which did not receive the transplant., Conclusions: Transplantation of AAV2-BDNF-IPE cells may be an alternative method of delivering neurotrophic factors to the lesion.