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Lien Veys, Marjan Vandenabeele, Veerle Baekelandt, Lieve K M Moons, Lies De Groef; The eye as a window to the brain: retinal characterization in a transgenic αSYN mouse model of Parkinson’s disease. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3105.
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© ARVO (1962-2015); The Authors (2016-present)
Although it is well-documented that many patients with Parkinson’s disease (PD) present with visual disabilities, scientific research on the impact of PD on the retina is lagging behind. Nevertheless, the unique properties of the eye in terms of transparency and accessibility make it attractive for (i) clinical research on PD symptoms and potential biomarkers in the eye; and (ii) fundamental research into PD disease mechanisms. In this study, we characterized α-synucleinopathy, including neurodegeneration and -inflammation, in the retina of (Thy-1)-h[A30P]αSYN mice.
Wild-type (WT) and (Thy-1)-h[A30P]αSYN transgenic mice at 15 months of age were studied using non-invasive in vivo imaging with optical coherence tomography (OCT), complemented with post mortem (immuno)histological analyses of αSYN localization, retinal histology, dopaminergic innervation and glial reactivity.
In αSYN mice yet not in WT animals, prominent αSYN expression was observed in both somata and neurites in the nerve fiber layer, ganglion cell layer, and inner plexiform layer; as well as in dispersed cell bodies in the inner nuclear layer. A fraction of this αSYN was phosphorylated and was found in sparse cell bodies in the ganglion cell layer. In vivo OCT imaging revealed thinning of the ganglion cell complex and thickening of the outer nuclear layer, as confirmed by post mortem morphometric analyses. Despite this retinal atrophy in the inner retina, cell counting in the ganglion cell layer did not disclose cell loss and immunostainings revealed no difference in the tyrosine hydroxylase expression between transgenic and WT animals. Finally, immunostainings for Iba-1 and GFAP showed unchanged microglial reactivity yet increased macroglial reactivity in the retina of αSYN mice versus WT controls, respectively. These data are in agreement with previous reports that described the presence of αSYN, lack of dopaminergic cell loss, and increased macroglial reactivity in the brain of this transgenic mouse model.
(Thy-1)-h[A30P]αSYN mice show retinal manifestations of α-synucleinopathy, including (i) αSYN depositions, (ii) inner retinal atrophy, (iii) outer retinal thickening, and (iv) increased macroglial reactivity. These findings mirror brain manifestations in this transgenic mouse line and emphasize that the retina can be used as a model organ for the CNS in studies of PD.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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