Abstract
Purpose :
Aging is a major risk factor of retinal thinning and RGC loss, both of which are also hallmarks of neurodegenerative diseases like MS. Considering the heterogeneity and uncertainty of MS pathogenesis, differential characterisation of RGC degeneration between normal aging and MS will help widen our understanding. Here, we used histological RGC counts from two age groups in both healthy and CPZ-MS mice to test the hypotheses that RGC loss is associated with typical aging and the neuropathology of the CPZ-MS model.
Methods :
Male C57 mice were fed chow mixed with 0.2%w/w CPZ for 16 weeks until 6 months (6mCPZ, n = 3) or 28 months old (28mCPZ, n = 4). Age-matched healthy mice (6mCtrl, n = 4; 28mCtrl, n = 3) were fed standard chow. Mice were culled and perfused with 4% paraformaldehyde. Both eyes were enucleated, and the retinas were dissected, immunostained for RGCs with RNA binding protein with multiple splicing (RBPMS), mounted on slides and then imaged. These whole retinal images were then run through an automated algorithm to quantify the RGC densities which were analysed with a 2-way ANOVA with age-group and disease group as between-subject factors.
Results :
There was a main effect of age (F (1, 10) = 36.13, p = 0.0001), disease state (F (1, 10) = 5.46, p = 0.04) and nosignificant interaction between age and disease state (F (1, 10) = 1.12, p = 0.31). Pairwise comparisons showed significantly lower RGC density in 28mCtrl vs. 6mCtrl (p = 0.0025) and in 28mCPZ vs. 6mCPZ (p = 0.025, Figure 1). Although not significant, there was numerically lower RGC density in in CPZ-MS vs. healthy conditions at 6m (p = 0.14) and 28m (p = 0.80).
Conclusions :
Our results suggest that CPZ-MS mice express fewer RGC than healthy controls. Both groups show a similar rate of age-related decline in RGC density. Previous reports state that 16-week CPZ exposure reflects a restorative stage of the model. Therefore, a comparative observation using shorter CPZ administration could be useful.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.