Graft Location Affects Functional Rescue Following RPE Cell Transplantation in the RCS Rat

Abstract

Photoreceptor (PRC) rescue in the dystrophic Royal College of Surgeons (RCS) rat has been well documented following a variety of interventions. Although the dystrophic process is asymmetric with respect to the horizontal meridian, little attention has been paid to the effect of topographic position on treatment outcome. In this study, RPE cells from adult congenic nondystrophic animals were injected into the subretinal space of 1-month-old dystrophic RCS rats in either the dorsal or the ventral equatorial region. Animals were followed longitudinally during the degenerative process using the pupillary light reflex (PLR). The parameter of the PLR most sensitive to PRC rescue is latency at low light levels. At 3 months of age this parameter showed statistically better performance (ANOVA, P = 0.016) for eyes with grafts placed dorsally compared to those placed ventrally or untreated controls. There was no treatment effect on amplitude. By 6 months of age the dorsal/ventral disparity in latency was less apparent and amplitude remained equivalent across groups. Late analysis of retinal whole-mounts using RT-97 fluorescent labeling showed extensive irregularities in ventral axonal morphology in all treatment groups. These results indicate that functional rescue of the RCS retina is significantly influenced by the local degenerative timetable. The role of initial local conditions on treatment outcome is worthy of consideration in other models of neuroprotection.