Photoreceptor degeneration in the RCS rat attenuates dendritic transport and axonal regeneration of ganglion cells

PURPOSE. Photoreceptor loss in the Royal College of Surgeons (RCS) rat depr ives the retinal ganglion cells (RGCs) of sensory input, which could interf ere with RGC physiology. Whether axonal and dendritic transport is altered, and whether RGCs retain their capacity to regenerate their axons, both in vivo and in culture, was ascertained. METHODS. The study was conducted at postnatal days (P) 30 (while most photo receptors are still intact), P90 (photoreceptors being almost completely ab sent), and P180 (approximately 3 months after photoreceptor disappearance). RGCs were studied with retrograde transport of the fluorescent dye 4Di-10A SP. Dendritic transport was also studied with 4Di-10ASP that is transported from the cell bodies into the RGC dendrites. Regeneration of RGC axons in vivo was monitored in the grafting paradigm of replacing the cut optic nerv e (ON) with a sciatic nerve (SN) piece. Cell counts were performed in retin al wholemounts. Axonal regrowth in vitro was assessed in organotypic cultur es of retinal stripes. RESULTS. Photoreceptor dystrophy did not adversely affect retrograde axonal transport but attenuated dendritic transport compared with the wild-type c ontrol rats. Axons of RGCs were able to regenerate if provided with a SN gr aft, and regeneration was observed to be similar between RCS and wild-type rats at P30 but differed significantly at P90 and P180. In addition to an a ge-dependent decline in the regenerative ability, seen also in control anim als, the number of RCS RGCs able to regenerate declined drastically beginni ng at 3 months. It is plausible that the intraretinal reorganization, as a consequence of photoreceptor disappearance, interferes with the regenerativ e ability of the RGCs. CONCLUSIONS. The findings suggest for the first time that diminution of pho toreceptor sensory input does not induce detectable death of RGCs until P18 0, but that it attenuates certain ganglion cell functions like intraretinal dendritic transport and propensity for axonal regeneration.