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Christine Tram Oanh Nguyen, Jeremiah K.H. Lim, Zheng He, Algis J Vingrys, Holly Rose Chinnery, Timothy Marc Ryan, Qiao-Xin Li, Bang V Bui; Amyloid-beta in the rodent retina exhibits a characteristic hyperspectral profile. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2215.
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© ARVO (1962-2015); The Authors (2016-present)
Alzheimer’s disease is characterised by the deposition of amyloid-beta (Aβ) plaques in the cortex which can be visualised in vivo using PET imaging. Recent evidence indicates the presence of Aβ in the retina, opening the possibility of cost-effective and non-invasive optical imaging of Aβ. Hyperspectral imaging is employed to evaluate whether retinal Aβ exhibits a signature profile.
Three Ab preparations underwent hyperspectral imaging from 320 to 680nm in 1nm steps (Polychrome V light source, cMOS camera). Firstly, isolated aggregating Aβ1-42 (in vitro Aβ) was compared against PBS vehicle (n=10/group). Secondly, this aggregated Aβ1-42 was intravitreally injected (5ul, in vivo exogenous) into a rat eye and compared to PBS vehicle injection (n=7/group). Finally, a transgenic mouse model of familial Alzheimer’s disease (5xFAD, in vivo endogenous) and wild-type littermates were imaged at 6 months old (n=7/group) under anaesthesia (60:5 mg/kg ketamine:xylazine). In transgenic mice, paraffin sections of brain tissues were stained with monoclonal Aβ antibodies (1E8, 1:200) and quantified using ELISA to assess Aβ content (Brain: n=6; Retina: n=6 pooled). Hyperspectral profiles normalised to peak reflectance were compared between groups using one-way ANOVA.
In vitro Aβ exhibits a higher reflectance between 411 to 508nm (p< 0.05) but a similar reflectance outside these wavelengths (<410nm or >509nm) compared with vehicle (p>0.05). Similarly, in vivo exogenous Aβ showed a preferentially higher reflectance over the band 409 to 481nm (p<0.05) compared with vehicle. Imaging of transgenic mice reveals a significant increase in relative reflectance over the band 459 to 488 nm (p<0.05). In transgenic mice, immunohistochemistry confirmed Aβ deposition in the hippocampus and cortex. ELISA finds Aβ deposition in brain and retina in 5xFAD mice (14.5±2.2, 14.5pg/mg respectively. This was not detectable in WT mice.
In vitro and in vivo exogenous preparations of Aβ exhibit similar hyperspectral reflectance profiles to 5xFAD mice, all producing consistent differences at 459 to 481nm when compared to their respective controls. This opens the possibility of using hyperspectral imaging as a non-invasive tool to detect Aβ in retina in the absence of contrast medium.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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