Age modulates the expression and phosphorylation profile of retinal tau. A, Representative Western blots of soluble retinal extracts from 2- and 8-month-old Brown Norway rats probed with an antibody against total tau (K9JA) demonstrated the presence of three predominant tau isoforms of 50, 55, and 100 kDa. B, Densitometric analysis showed a 1.7-fold and 2.8-fold increase in the 50 and 100 kDa tau variants, respectively, in samples from 8-month-old animals (N = 6) compared with younger animals (N = 3; Student's t test, *p < 0.05). C, D, All tau isoforms were observed in Tau+/+ mouse retinas (N = 3), whereas no signal was detected in Tau −/− murine retinal samples (N = 3), validating the specificity of the antibody. E–J, Analysis of phospho-specific tau epitopes demonstrated age-dependent changes in phosphorylation with PHF1 (Ser396, Ser404) and PS199 (Ser199), while no change was detected with AT8 (Ser202, Thr205; 8 month-old, N = 6; 2 month-old, N = 3; Student's t test, *p < 0.05). Vertical lines represent nonconsecutive samples from the same gel.