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António Francisco Ambrósio, Samuel Chiquita, Catarina Neves, Rafael Carecho, Filipa Baptista, Elisa Campos, Paula Moreira; Can the retina be used as a reliable mirror to evaluate changes occurring in the Alzheimer’s brain?. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5862.
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© ARVO (1962-2015); The Authors (2016-present)
Diagnosis of Alzheimer’s disease (AD) is difficult and relies on expensive and invasive methods. Since many AD patients experience early visual problems, the retina is an appealing source of information for AD diagnosis. We intend to clarify whether the retina is early affected and could be considered a reliable mirror of the brain alterations of an AD mice model.
Male triple transgenic (3xTg-AD; AD model) and age-matched wild-type (WT; C57BL6/129S) mice (4 and 8 months old; early time points) were used to evaluate retinal structural and functional changes by optical coherence tomography (line and circular scans), electroretinography (ERG; scotopic, photopic, and photopic flicker) and pattern ERG (PERG). Retina, hippocampus and total cortex homogenates (4 months old mice) were used to evaluate synaptic loss and glial reactivity by Western blot.
At 8 months, but not at 4 months, there was a significant reduction of retinal thickness of 3xTg-AD mice compared with WT, assessed with line scans (179.96±1.07 µm vs 188.60±2.34 µm) and circular scans (176.49±1.28 µm vs 186.75±2.36 µm). This reduction was detected in several layers, including ganglion cell layer. At 4 and 8 months there was also an increased (p<0.05) scotopic and photopic b-wave amplitude and photopic flicker amplitude (1st and 2nd harmonic) in 3xTg-AD mice. No differences were detected in PERG recordings between 3xTg-AD and WT mice.At 4 months, there was a significant increase in the levels of amyloid beta (Aβ) and p-Tau in the hippocampus (287.97±57.23% and 198.77±39.89% of WT, respectively) and total cortex (220.23±37.70% and 166.10±15.624% of WT, respectively), but not in the retina, of 3xTg-AD mice. The levels of β-secretase and choline acetyltransferase were not affected in the three regions analyzed. There was a significant increase of glial fibrillary acidic protein, but only in the hippocampus of 3xTg-AD mice (212.18±27.01% of WT). The synaptic proteins synaptophysin and syntaxin were unchanged in these three regions, with the exception of syntaxin levels (increased in the cortex of 3xTg-AD mice).
This study shows that at early stages (4 and 8 months) the brain (hippocampus and/or cortex) of 3xTg-AD mice is more affected than the retina, but the retina is also affected, and so changes in the retina might be used for AD diagnostics.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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