BACKGROUND Replacement of degenerating retinal pigment epithelial (RPE) cells has been proposed to promote photoreceptor survival in retinal pigment epithelial disease. However, allografts of RPE have a higher rate of immunological rejection. The investigators studied the effects of autotransplantation of RPE on the morphological changes in photoreceptors and choriocapillaris. METHODS RPE autotransplantation (wound type 1) was performed in 25 rabbits and compared with wounds following debridement of the RPE (wound type 2). Light and electron microscopy and scanning electron microscopy of choroidal vascular casts were performed at 3, 7, 14 and 30 days after surgery. Quantitative analysis of the choriocapillaris bed area was performed by automated image analysis and the results were analyzed by paired Student's t-test. RESULTS Retinal pigment epithelium was found to be monolayered and ill-differentiated at day 7. Differentiation occurred at day 30, with preservation of photoreceptors and other layers of the neurosensory retina in type 1 wounds. Type 2 wounds showed atrophy of the regenerating retinal pigment epithelium at day 14 and day 30 with loss of overlying photoreceptor cell layer. There was significant choriocapillaris regeneration in type 1 wounds compared to the type 2 wounds at day 7 (P=0.045), day 14 (P=0.028) & day 30 (P=0.06). CONCLUSIONS Retinal pigment epithelial autotransplantation significantly reduced photoreceptor degeneration and choriocapillaris atrophy associated with loss of retinal pigment epithelium. This procedure supports the hypothesis that RPE autotransplantation may be helpful in geographic atrophy and conditions requiring submacular surgery.