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Daniel L Chao, Jonathan H Lin, David Castillejos, Karen Chiang, Nobu Hiramatsu, Allen Chen, Edward Koo; Retinal and optic nerve dysfunction in PS19 tau transgenic mice. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3112.
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© ARVO (1962-2015); The Authors (2016-present)
Tau accumulation in the central nervous system has marked deleterious effects in spinal cord and brain, however its effect on the optic nerve and the retina is less clear. PS19 tau transgenic mice, which overexpress the human 1N4R tau isoform with a P301S mutation, have previously been shown to express abundant levels of pathological hyperphosphorylated tau in the optic nerve, photoreceptors, and retinal ganglion cells. In order to/To understand retinal phenotypes in tauopathies more fully, we characterized the retinal and optic nerve structure and function of aged PS19 mice through electroretinography (ERG), spectral domain optical coherence tomography (SD-OCT), histology, and molecular biology.
12-month-old PS19 mice and age-matched controls underwent scotopic and photopic ERG testing to investigate both cone and rod functionality. Immunohistochemical staining of human tau, phospho-tau, GFAP, Iba1, and synaptophysin was performed on the mouse retinas and optic nerves, while hematoxylin and eosin (H&E) staining was also performed for anatomic analysis of the retina. Western blotting and qPCR were also used to analyze the levels of ER stress markers in retinal lysates.
The PS19 mouse retinas, when compared to age-matched controls, showed increased expression of pathological phospho-tau. The PS19 mice also showed a statistically significant increase in GFAP signal in optic nerves consistent with increased astrocytosis. However, the PS19 mice showed no changes in retinal thickness measured via H&E staining, and no difference in the amplitude of either photopic or scotopic ERG responses when compared to wild type controls. The expression of ER stress markers was also relatively unchanged between wild-type and PS19 mice.
Our results identify mild optic nerve pathology in PS19 mice. By contrast, rods and cones appear to be spared despite pathologic tau expression, and the retina as a whole did not exhibit degeneration or significantly increased astrocytosis and microgliosis. This suggests that tau pathology in PS19 mice has a much milder effect on the function of the retina than the brain.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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