Retinitis Pigmentosa is a group of hereditary diseases with rod photoreceptors degeneration, which is followed by central cone degeneration in the advanced stage. The patients experience night blindness and the progressive loss of visual field. Since the retinal bipolar cells that receive signals from the dying photoreceptors remain for a while, one therapeutic approach is to supply the photoreceptors to reconstruct initial visual transmission to these bipolar cells. We previously showed that mouse ES or iPS-derived retinas can develop structured photoreceptor layers after transplantation and the proximal presence of pre- and post-synaptic markers of the host photoreceptors and the graft bipolar cells were confirmed either by immunohistochemistry or genetic labeling. Evident light responsive activities of host retinal ganglion cells (RGC) were recorded by multiple electrode array system (MEA) over the grafted area in the retinas of end-stage retinal degeneration mice (rd1) that has only few remaining activities. Behavior test results also suggested the recovery of light perception in these mice after transplantation. Human ES/iPS retinas can also develop photoreceptor layers after transplantation in immune-deficient end stage retinal degeneration models such as NOG-rd1 or rhodopsin mutant SD-Foxn1 Tg(S334ter)3LavRrrc nude rats with some synaptic contact between the host and the graft by immunohistochemistry. We are preparing clinical trials using iPS-derived retinas.

To: 要旨(抄録)