Sectorial loss of retinal ganglion cells in inherited photoreceptor degeneration is due to RGC death

AIMS: To investigate the cause of retinal ganglion cell (RGC) loss in dystrophic aged Royal College of Surgeons (RCS) rats. METHODS: RCS-p+ (dystrophic) female rats of postnatal times (P365, P450 and P540) and age-matched RCS-p1 rdy+ (non-dystrophic) rats were used. In whole-mounted retinas, RGCs were doubly labelled with Fluorogold (FG) retrogradely transported from the superior colliculi and Brn3a immunohistochemistry. RGC axons were labelled with anti-neurofilament antibodies. Automatic image analysis techniques allowed quantification of the total population of RGCs per retina and construction of isodensity maps to investigate RGC topology. RESULTS: Dystrophic retinas showed at all times studied wedge-shaped sectors devoid of FG(+) and Brn3a(+) RGCs. These sectors were also devoid of neurofilament-labelled axons. The total number of FG(+)RGC and Brn3a(+)RGC per retina was significantly smaller in dystrophic rats at P540, revealing RGC death at this age. The total number of FG(+)RGCs was smaller than those of Brn3a(+)RGCs at P540, indicating a disturbance of the retrograde axonal transport at this age. CONCLUSIONS: RGC double labelling documents that sectorial RGC loss in aged dystrophic RCS rats is mainly due to RGC death, although a deficit of the retrograde axonal transport exists also at the more advanced ages.