High expression of CM results in progressive loss of photoreceptor cells. A, The thickness of the ONL in the central, middle, and peripheral retina of mice at indicated ages. Two-way ANOVA with genotype and age as main factors revealed significant effects of genotype in the central (F(5,96) = 51, p < 0.0001), middle (F = 20.5, p < 0.0001), and peripheral (F = 11.77 p < 0.0001) retina. The effect of age was also significant in all retinal subdivisions (p < 0.001). The decline in the ONL thickness with age was more apparent in CM271arr−/− and CM292arr−/− lines, as evidenced by the significant genotype × age interaction (p < 0.0001 for the central and middle retina; p = 0.0012 for the peripheral retina). ***p < 0.001 to WT; $p < 0.001 to CM77arr−/−, CM111arr−/−, and CM175arr−/−; ∧p < 0.01 to CM77arr−/−, according to Bonferroni post hoc comparison for each retinal subdivision and age. The symbols are color coded to refer to CM271arr−/− or CM292arr−/− lines. N = 5 mice/genotype/age. B, The length of the OS in the central, middle, and peripheral retina of mice at indicated ages. Two-way ANOVA with genotype and age as main factors revealed significant effects of genotype in the central (F(5,96) = 224, p < 0.0001), middle (F = 104, p < 0.0001), and peripheral (F = 97 p < 0.0001) retina. The effect of age was significant in all retinal subdivisions (p < 0.0001; as was the genotype × age interaction, p < 0.0001). The statistical significance of the differences is shown, as follows: *p < 0.05, ***p < 0.001 to WT; $p < 0.001 to CM77arr−/−, CM111arr−/−, and CM175arr−/−; #p < 0.01 to CM77arr−/− and CM111arr−/−, and p < 0.05 to CM175arr−/−; @p < 0.01 to CM175arr−/− and CM111arr−/−; !p < 0.001 to CM271arr−/−, according to Bonferroni post hoc comparison following separate one-way ANOVA for each retinal subdivision and age. N = 5 mice/genotype/age. Representative sections showing ONL and OS in different lines are presented in Figures 9 and 10, respectively.