Photoreceptor degeneration in the RCS rat attenuates dendritic transport and axonal regeneration of ganglion cells.
OBJECTIVE
Photoreceptor loss in the Royal College of Surgeons (RCS) rat deprives the retinal ganglion cells (RGCs) of sensory input, which could interfere 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 photoreceptors are still intact), P90 (photoreceptors being almost completely absent), and P180 (approximately 3 months after photoreceptor disappearance). RGCs were studied with retrograde transport of the fluorescent dye 4Di-10ASP. 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 nerve (ON) with a sciatic nerve (SN) piece. Cell counts were performed in retinal wholemounts. 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 compared with the wild-type control rats. 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 RGCs able to regenerate declined drastically beginning at 3 months. It is plausible that the intraretinal reorganization, as a consequence of photoreceptor disappearance, interferes with the regenerative ability of the RGCs.


CONCLUSIONS
The findings suggest for the first time that diminution of photoreceptor sensory input does not induce detectable death of RGCs until P180, but that it attenuates certain ganglion cell functions like intraretinal dendritic transport and propensity for axonal regeneration.
Pavlidis
M
M
Department of Experimental Ophthalmology, School of Medicine, University of Münster, Germany.
Fischer
D
D
Thanos
S
S
D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D001369:Axons / Q000502:physiology*; D002452:Cell Count; D003712:Dendrites / Q000502:physiology*; D005260:Female; D005456:Fluorescent Dyes / Q000378:metabolism; D008297:Male; D009416:Nerve Regeneration / Q000502:physiology*; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology*; D051381:Rats; D011922:Rats, Mutant Strains; D012162:Retinal Degeneration / Q000473:pathology / Q000503:physiopathology*; D012165:Retinal Ganglion Cells / Q000502:physiology*
D005456:Fluorescent Dyes