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Léa Rodriguez, Julius Baya Mdzomba, Mélissa Boudreau-Laprise, Sandrine Joly, Vincent Pernet; Human tau expression exerts beneficial effects on the mouse retinal function. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5522.
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© ARVO (1962-2015); The Authors (2016-present)
Tau is a protein implicated in the stabilization of microtubules in the axon. Its hyperphosphorylation is a hallmark of Alzheimer’s disease (AD). Human Tau expression in the mouse brain is sufficient to induce AD. In the current study, we evaluated the effects of human Tau on retinal function, histology and cell signaling during aging.
Mice deficient in murine Tau expression (mTKO) and transgenic mice expressing only human Tau isoforms (mTKO-hTau) were examined at 5 and 17 months of age. The retinal function was tested by electroretinogram (ERG) recordings in scotopic and photopic conditions. The activation of neurons in the visual cortex was assessed by visual evoked potential (VEP) recordings. The expression level of phospho-Tau (P-Tau), total Tau, retinal cell markers and signaling pathway molecules was observed by immunofluorescence on histological sections and by Western blotting in retinal lysates. Signaling cascade activations were compared with protein samples from hippocampi and cerebral cortices. RGC survival was evaluated on retinal flat-mounts stained for RBPMS.
Tau and P-Tau were localized in the cytoplasm of RGCs, bipolar and photoreceptor cells of mTKO-hTau retinae. In scotopic condition, ERG measurements showed no difference in b and a-wave amplitudes between mTKO and mTKO-hTau. However, the stimulation of blue cones with UV flashes induced higher ERG b-wave amplitudes in mTKO-hTau than in mTKO mice at 5 months. No difference was observed in VEP recordings. Surprisingly, hTau expression did not impair RGCs survival during aging. On retinal sections, PKCa, S-opsin and M-opsin immunostainings did not show hTau-induced changes in the inner nuclear and outer nuclear layers compared with mTKO littermates. Strikingly, Western blot analysis revealed a significant upregulation in P-mTOR in mTKO-hTau retinae compared to mTKO. In comparison with the hippocampus and the cortex, mTKO-hTau retinae displayed a significantly higher level of P-Tau, P-mTOR, and P-AKT.
Our results showed that human Tau expression does not activate neurodegenerative processes in the retina, contrary to what has previously been reported in the brain of mTKO-hTau mice. The positive effects of hTau on the ERG response may be due to signaling pathway modulation by Tau in photoreceptors and bipolar cells.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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