Visual impairments, such as difficulties in reading and finding objects, perceiving depth and structure from motion,
and impaired stereopsis, have been reported in tauopathy disorders, such as frontotemporal dementia (FTD). These
impairments however have been previously attributed to cortical pathologies rather than changes in the neurosensory
retina or the optic nerve. Here, we examined tau pathology in the neurosensory retina of the rTg(tauP301L)4510
mouse model of FTD. Optic nerve pathology in mice was also assessed using MRI, and corresponding measurements
taken in a cohort of five FTD sufferers and five healthy controls. rTg(tauP301L)4510 mice were imaged (T2-weighted
MRI) prior to being terminally anesthetized and eyes and brains removed for immunohistochemical and histological
analysis. Central and peripheral retinal labelling of tau and phosphorylated tau (pTau) was quantified and retinal layer
thicknesses and cell numbers assessed. MR volumetric changes of specific brain regions and the optic nerve were
compared to tau accumulation and cell loss in the visual pathway. In addition, the optic nerves of a cohort of healthy
controls and behavioural variant FTD patients, were segmented from T1- and T2-weighted images for volumetric study.
Accumulation of tau and pTau were observed in both the central and peripheral retinal ganglion cell (RGC), inner
plexiform and inner nuclear layers of the neurosensory retina of rTg(tauP301L)4510 mice. This pathology was
associated with reduced nuclear density (− 24.9 ± 3.4%) of the central RGC layer, and a reduced volume (− 19.3 ± 4.6%)
and elevated T2 signal (+ 27.1 ± 1.8%) in the optic nerve of the transgenic mice. Significant atrophy of the cortex
(containing the visual cortex) was observed but not in other area associated with visual processing, e.g. the lateral
geniculate nucleus or superior colliculus. Atrophic changes in optic nerve volume were similarly observed in FTD
patients (− 36.6 ± 2.6%). The association between tau-induced changes in the neurosensory retina and reduced optic
nerve volume in mice, combined with the observation of optic nerve atrophy in clinical FTD suggests that ophthalmic
tau pathology may also exist in the eyes of FTD patients. If tau pathology and neurodegeneration in the retina were to
reflect the degree of cortical tau burden, then cost-effective and non-invasive imaging of the neurosensory retina
could provide valuable biomarkers in tauopathy. Further work should aim to validate whether these observations are
fully translatable to a clinical scenario, which would recommend follow-up retinal and optic nerve examination in FT