Spatiotemporal pattern of rod degeneration in the S334ter-line-3 rat model of retinitis pigmentosa

We have recently described the surviving cones and Muller-glia process remodeling in retinitis pigmentosa (RP) and shown that rod degeneration triggers the reorganization of the cone mosaic into an orderly array of rings. Within these rings, remodeled Muller-glia processes envelope cones. Here, we report the spatiotemporal pattern of healthy rods, their relationship with dying rods and the way that rod death stimulates the modification of cone spatial-distribution patterns and Muller-glia processes in the S334ter-line-3 rat, a transgenic model expressing a rhodopsin mutation that causes RP. The spatial patterns of rods, cones, microglial and Muller cells were labeled by immunocytochemistry with cell-type-specific markers at various stages of deveopment in rat whole-mount retinas. Spatial patterns of dying cells were examined by TUNEL staining. The S334ter rod mosaic began to develop small holes around postnatal day 10. These hot-spots of cell death progressively increased in size, leaving larger rod-less holes behind. The holes were temporarily occupied by active microglial cells, before being replaced by remodeled Muller-cell processes. Our data suggest that the hot spots of rod death create holes in the rod mosaic early in retinal degeneration and that the resulting pattern triggers the modification of the spatial-distribution patterns of cones and glia cells.