Retinal ganglion cell numbers and delayed retinal ganglion cell death in the P23H rat retina

The P23H-1 rat strain carries a rhodopsin mutation frequently found in retinitis pigmentosa patients. We investigated the progressive degeneration of the inner retina in this strain, focussing on retinal ganglion cells (RGCs) fate. Our data show that photoreceptor death commences in the ventral retina, spreading to the whole retina as the rat ages. Quantification of the total number of RGCs identified by Fluorogold tracing and Brn3a expression, disclosed that the population of RGCs in young P23H rats is significantly smaller than in its homologous SD strain. In the mutant strain, there is also RGC loss with age: RGCs show their first symptoms of degeneration at P180, as revealed by an abnormal expression of cytoskeletal proteins which, at P365, translates into a significant loss of RGCs, that may ultimately be caused by displaced inner retinal vessels that drag and strangulate their axons. RGC axonal compression begins also in the ventral retina and spreads from there causing RGC loss through the whole retinal surface. These decaying processes are common to several models of photoreceptor loss, but show some differences between inherited and light-induced photoreceptor degeneration and should therefore be studied to a better understanding of photoreceptor degeneration and when developing therapies for these diseases.

Research highlights
► We have investigated the state of the inner retinal layers in P23H-1 rats, focusing mainly in retinal ganglion cells (RGCs).
► We document quantitatively for the first time that P23H-1 rats have less RGCs than their homologous Sprague–Dawley rats. We also document that, once photoreceptor loss is complete due to the rhodopsin mutation, there are morphological changes in the inner retinal layers that cause RGC degeneration possibly by axonal compression.
► Although other authors had suggested RGC degeneration in P23H rats, it is the first time that this has been quantitatively documented.
► Furthermore, we document the cause of RGC degeneration in these animals.
► Finally, we also show that, while some of the morphological abnormalities found in the retinas of P23H-1 rats are common to several models of photoreceptor loss, others are different and should therefore be investigated to increase our understanding of photoreceptor degeneration and when developing therapies for these diseases.