Abstract
Purpose: :
To examine whether the P23H rhodopsin mutation results in axonal compression and death of retinal ganglion cells (RGCs), as observed in other light-induced (Marco-Gomariz et al, J. Comp. Neurol. 498(2006):163-179; García-Ayuso et al, IOVS 50 (2009): E-abstract 3612) or inherited (RCS-p+ rat) photoreceptor degenerations (Villegas-Pérez et al, J. Comp. Neurol. 392(1998):58-77).
Methods: :
P23H-1 homozygous albino rats at post-natal day (P) 30,90,180,270 and 365 and albino Sprague-Dawley (SD) rats at P60 and P365 were used for this study. RGCs were identified by Fluoro-Gold (FG) tracing, applied to the superior colliculli, or by Brn3a immunodetection. RGC axons were immunolabeled with RT97 and the retinal vessels were labelled with horseradish peroxidase. Retinas were processed for whole mounts or cross-sections and examined and photographed using light and 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 counted in each retina using the same software (Salinas-Navarro et al, Vision Res. 49(2009):115-126, Nadal-Nicolás et al, IOVS 50(2009):3860-3868).
Results: :
P23H-1 rats exhibited progressive photoreceptor loss with age which was more marked in the ventral retina. At P180, only a few photoreceptor nuclei remained in the retinas and there was compression of the nerve fiber layer axons by the innermost retinal vessels. The number of FG-labeled or Brn3a positive RGCs gradually decreased with survival time. Because the numbers of cells labelled with FG or Brn3a were similar in the experimental retinas, this decrease must be the result of RGC death and not of an axonal transport deficit.
Conclusions: :
P23H rhodopsin mutation affects, with time, all retinal layers, causing vascular and axonal alterations and RGC death at a similar rate to that previously described in other inherited or induced photoreceptor degenerations. These events are thus, secondary to photoreceptor degeneration and not inherent to the disease.
Keywords: retinal degenerations: hereditary • retina: proximal (bipolar, amacrine, and ganglion cells) • nerve fiber layer