Selective transplantation of rods delays cone loss in a retinitis pigmentosa model

Background: Rod-cone retinal degenerations (retinitis pigmentosa) are typified by initial rod loss followed by secondary cone death. Rod death, predominantly caused by gene mutations expressed specifically in these cells, induces scotopic vision loss. Cone death, the overriding cause of blindness, has no current explanation. Disease progression and preliminary data suggest that cone survival depends on rods. Objective: To establish whether rod transplantation into mutant rodless retinas could halt cone loss. Methods: We transplanted pure sheets of rods isolated from normal-sighted mice into the subretinal space of recipient retinal degeneration mice lacking rods but possessing approximately 30% residual cones. Control animals were unoperated on or grafted with inner retinal cells from young normal donors, entire retinas from aged retinal degeneration mice, or gelatin. Two weeks after surgery, we quantified by an unbiased method the numbers of host retinal cones after immunolabeling with specific markers. Results: Only mice receiving rod-rich transplants demonstrated statistically significant greater cone numbers, with rescue of 40% of host cones normally destined to die during this period. Conclusion: Cone survival depends specifically on rods. Clinical Relevance: Such findings indicate that transplantation of rods could limit loss of cones, thus preserving useful vision in human retinitis pigmentosa.