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.