Sectorial Loss Of Retinal Ganglion Cells In The RCS Rat

Abstract

Purpose: : To investigate whether the sectorial loss of retinal ganglion cells (RGC) observed in previous studies of our laboratory in the dystrophic Royal College of Surgeons (RCS) rat strain (Villegas-Pérez et al., J Comp Neurol 1998;392: 58-77) is due to an axonal transport deficit problem or to retinal ganglion cell death.

Methods: : Dystrophic (rdy–/p+) and non-dystrophic (rdy+/p+) pigmented RCS rats with ages ranging from 12 to 20 months were used for this study. RGCs were identified using Fluoro-Gold (FG) tracing from the Superior Collicullus (SC), to label RGCs with a competent axonal transport and Brn3a immnunodetection, to detect all RGCs. Retinas were processed as whole mounts and examined by fluorescence microscopy. Reconstructions of the whole mounts were made using Image-Pro Plus 5.0 for Windows®. FG-labelled and Brn3a positive RGCs were automatically identified and counted in each retina using previously described methods (Salinas-Navarro et al., Vision Res. 2009;49: 115-126, Nadal-Nicolás et al., IOVS 2009;50: 3860-3868).

Results: : Dystrophic retinas showed with age wedge-shaped sectors devoid of both FG labelling and Brn3a detection. These sectors were observed first in the ventral retina and later spread dorsally. The number of both FG-labelled and Brn3a positive RGCs declined with age. However, at 20 months of age there were significantly higher numbers of Brn3a positive than of FG-labelled RGCs. Taken together, these data indicate that the sectors are due to RGC death, which is preceded by an axonal transport deficit.

Conclusions: : Sectorial RGC loss in the dystrophic RCS rat retina is due to an axonal transport deficit that ultimately causes RGC death.

Keywords: retinal degenerations: hereditary • ganglion cells • degenerations/dystrophies