Water escape as a tool to demonstrate functional advantage following retinal transplantation

Purpose: Transplantation of human fetal retinal pigment epithelial (RPE) cells have been shown to rescue degenerating photoreceptors in the RCS rat. This study uses a water maze paradigm as a tool to assess post transplantation changes in behavior associated with a visual stimulus. Methods: Five dystrophic RCS rats received bilateral injections of freshly isolated human fetal RPE cells into the subretinal space of the superior equatorial hemisphere. Five age-matched control dystrophic RCS rats received injections of vehicle. All animals were immunosuppressed. At two months post transplantation, each rat was tested in the water escape apparatus. The rat used a single light source, randomly located on the edge of the lank, to locate a submerged platform, placed directly in front of the light. Each rat was timed and videotaped during ten consecutive trials. The swimming paths and times for all rats were statistically analyzed. Subsequent to the water escape trials, the eyes were embedded for histologie analysis which included quantitative assessment of photoreceptor cells in predefined retinal regions. Results: The water escape data indicated the differences between the sham and experimental groups changed significantly over time (p=0.0017). Over time, the transplanted animals learned to use light as a clue (p<0.0001); whereas the sham animals did not (p=0.73). Transplanted eyes had a significant greater mean number of photoreceptors in the superior, grafted region than seen in the inferior region of the same eyes and as compared with either region of sham-injected eyes (p=0.0023). Conclusions:: Statistical analyses demonstrated a functional advantage for visuallyguided behavior in RCS rats transplanted with human fetal RPE cells and a statistically significant PRC rescue effect at two months after transplantation Supported by Dr. Sam Williams, Research to Prevent Blindness, and the Rochester Eye Bank.