V 103Transneuronal effects of the photorezeptor degeneration in the RCS-rat strain at the deafferentiated retinal ganglion cells
M. Pavlidis, D. Fischer, S. Thanos
Purpose: Photoreceptor loss in the Royal-College of Surgeons (RCS) rat deprives the retinal ganglion cells (RGCs) of sensory input, which could interfere with RGCs physiology. We aimed to ascertain whether axonal and dendritic transport is altered, whether RGCs responce to optic nerv injury and whether RGCs retain their capacity to regenerate their axons, both in vivo and in culture.
Methods: The study was conducted at postnatal days P30 (while most photoreceptors are still intact), P90 (photoreceptors being almost completely absent) and P180 (about 3 months after photoreceptor disappearance). RGCs were studied with retrograde transport of the fluorescent dye 4Di-10ASP. Dendritic transport was also studied with 4Di-10 ASP that is transported from the cell bodies into the RGC-dendrites. Vulnereability of RGCs was observed after SC labeling and optic nerv axotomy.Regeneration of RGC-axons in vivo was monitored in the grafting paradigm of replacing the cut optic nerve with a sciatic nerve (SN) piece. Cell counts were performed in retinal whole mounts. Axonal regrowth in vitro was assessed in organotypic cultures of retinal stripes.
Results: Photoreceptor dystrophy did not adversely affect retrograde axonal transport, but attenuated dendritic transport as compared to the wild type control rats. A higher RGCs vulnereability to axotomy has been observed. Axons of RGCs were able to regenerate if provided with a SN- graft, 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 age-dependent decline in the regenerative ability, seen also in control animals, the number of RCS-rat ganglion cells able to regenerate, declined drastically beginning at three months. It is plausible that the intra-retinal reorganisation, as consequence of photoreceptor disappearance, interferes with the regenerative ability of the retinal ganglion cells.
Conclusions: The findings suggest for the first time, that diminution of photoreceptor sensory input does not induce detectable death of RGCs until P180, but attenuates certain ganglion cell functions like intra-retinal dendritic transport, surviving after optic nerv injury and propensity for axonal regeneration.
Univ. Eyeklinik, Experimental-Ophthalmology, Domagstr. 15. D-48149, Münster