Abstract
Purpose:
To determine whether C1q ablation has a protective effect on retinal ganglion cell (RGC) and axonal loss in glaucoma.
Methods:
Congenic C1q Knockout (KO) mice were generated in the DBA/2NNia background. Female and male KO, Heterozygous (HT) and Wild type (WT) mice were aged. IOPs were recorded in a subset of animals. Retinas of mice from all three groups at 6, 9 and 12 months of age were flat mounted after retrograde labeling, imaged and scored semi quantitatively on a 10 point scale by two independent observers. Semi-thin sections of optic nerves (ON) were also graded for the amount of axonal damage semi quantitatively, by two masked observers. One way analysis of variance (ANOVA) with Bonferroni’s post-hoc test was used for statistical analysis in the study.
Results:
Female KO and HT mice had significantly higher IOP (ANOVA, P<0.05) between 6 and 12 months of age compared to WT animals. No differences in IOPs between animals of the three genotypes were observed in males (ANOVA, P>0.05). At 6 months of age, there was no difference in retinal or optic nerve scores between the three groups (KO, HT, WT; ANOVA, P>0.05 for both RGC and ON) in animals of either sex. At 9 months of age, female mice didn’t show significant differences in retinal or ON scores between KO, HT and WT (ANOVA, P>0.05 for both RGCs and ONs). However, male KO and HT mice had better RGC and ON scores (ANOVA, P<0.05 for both RGCs and ONs) compared with WT mice. At 12 months of age, both male and female C1q KO had better RGC scores (ANOVA, P<0.05 for both sex) compared to WT and HT but ON scores were not differerent between all three genotypes in animals of either sex (ANOVA, P>0.05 for both sexes).
Conclusions:
Absence of C1q ameliorates RGC and ON loss in the DBA/2 mice but this effect differs by sex and is probably modulated by IOP.