Abstract
Purpose :
Tau is a microtubule-associated protein that has been involved in glaucoma. Its physiological function in the visual system is unknown. The aim of this study was to investigate the contribution of Tau to the maturation and the plasticity of the intact mouse visual system.
Methods :
Western blotting and immunofluorescent analysis of Tau isoform (T3R and T4R) expression were performed on retinae and visual cortices from postnatal day 1 (P1) to P360. To induce visual plasticity, monocular deprivation (MD) was realized by suturing right eyelids. After 5 days of MD, the expression of Tau isoforms, Erk, a modulator of neuronal plasticity, and acetylated tubulin, a microtubule instability marker, was followed in the visual cortex (VC) by Western blotting. Visual function was assessed by electroretinogram (ERG) recordings, optokinetic reflex (OKR) and visual evoked potential (VEP) recordings in the left binocular VC in response to left and right eye stimulations, in young adult (3-5 months) and old (20-24 months) WT and Tau knockout (Tau KO) mice. VEPs were used to calculate an ocular dominance index (ODI). Retinal ganglion cell (RGC) survival was quantified on retinal flat-mounts.
Results :
In the first postnatal month, T3R downregulation and T4R upregulation in retinal and VC lysates were associated with the decline in neuronal plasticity occurring during the critical period. ERG recordings and RGC survival showed no difference between WT and Tau KO during aging. The OKR of Tau KO vs WT did not differ. In contrast, the ODI was significantly weaker in Tau KO than in control WT. In MD mice, Western blot and immunofluorescent analyses revealed increased expression of Tau isoforms in the VC of the deprived eye, suggesting an implication of Tau in visual plasticity. The rise in OKR sensitivity induced by MD was statistically higher in Tau KO than in WT during aging, suggesting that Tau limits the activation of neuronal plasticity in the VC. After MD, the ODI of Tau KO was similar to that of WT and to nondeprived Tau KO. Western blot results showed increased levels of Erk in Tau KO relative to WT mice. Interestingly, the Tau KO cortex contained less acetylated tubulin, indicating possible increased microtubule instability in the absence of Tau.
Conclusions :
Our results suggest a new function for Tau in the adaptive plastic mechanisms operating in the adult visual brain subjected to sensory experience changes. Tau may limit visual plasticity in adult mice.
This is a 2021 ARVO Annual Meeting abstract.