Ophthalmology (Eye & Ear Hospital) - Research Publications

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Start date: 2010 × End date: 2019 × Type: Abstract × Author: van Wijngaarden, Peter ×

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    A retinal imaging biomarker of Alzheimer's disease
    van Wijngaarden, P ; Hadoux, X ; Hui, F ; Lim, J ; Nguyen, C ; Bui, B ; Crowston, J (Wiley, 2019-11-01)
    Background: Amyloid-beta (Ab) deposition in the brain is a diagnostic marker for Alzheimer's disease (AD), but current tests are costly and not widely available. Evidence from transgenic rodent models and post-mortem human tissues suggest that retinal accumulation of Ab may serve as a surrogate marker of brain Ab levels. As Ab has a wavelength-dependent effect on light scatter, we investigated the potential for in vivo retinal hyperspectral imaging to serve as a biomarker of brain Ab. Purpose: To develop and validate a retinal imaging biomarker of Alzheimer's disease. Methods: We performed human retinal hyperspectral imaging on individuals with high Ab burden on brain PET imaging and mild cognitive impairment (cases; n = 15), and age-matched PET-negative controls (n = 20). Image analysis methods were developed and validated on a second group of participants with and with (n = 4) and without (n = 13) moderate-to-high brain Ab burden and on transgenic mice (5xFAD) known to accumulate retinal Ab. Results: We show significant differences in retinal reflectance spectra between cases and controls in both cohorts (AUC ROC = 0.82, P = 0.001, 95% CI: 0.67-0.97). There was a moderate positive linear correlation between retinal imaging scores and brain Abburden (r = 0.46, 95%CI: 0.13-0.69, P = 0.008).The technique also enabled discrimination of AD-model mice from wild-type controls. Conclusion: We have developed a novel retinal imaging method to distinguish people with moderate-high brain Ab load from those without. This approach may have value for the diagnostic confirmation of AD.
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    A tractable preclinical model of optic nerve demyelination
    van Wijngaarden, P ; Paul, JP ; Wong, VHY ; Bui, BV ; Merson, TD (Association for Research in Vision and Ophthalmology, 2019-07-01)
    Purpose : Progress in the development of therapies to enhance remyelination in demyelinating diseases has been hampered by a lack of appropriate preclinical models - functional measures are often lacking or variable. We sought to develop a tractable and reproducible model of optic nerve demyelination with precise structural and functional measures. Methods : Oligodendrocytes of MBP-DTR 100a transgenic mice express diphtheria toxin receptor (DTR) and systemic diphtheria toxin (DT) administration induces diffuse demyelination of the central nervous system. In the present study we used retrobulbar DT injection to induce focal demyelination of the optic nerves of 3-month-old MBP-DTR 100a mice. Dose optimisation: anaesthetised mice underwent unilateral retrobulbar DT injection with 5, 10 or 15ng/kg DT (n=7 per dose, 1 µL per injection). Tissues were harvested three weeks after injection. Time-course study: Following baseline visual evoked potential (VEP) recording, electroretinogram (ERG) and optical coherence tomography (OCT), mice underwent retrobulbar DT injection with 15ng/kg DT or 1µL PBS. Follow-up measurements were taken at 2 (n=5 DT, 5 PBS), 4 (n=6 DT, 6 PBS), 8 (n=9 DT, 9 PBS) or 12-weeks (n=7 DT, 7 PBS). Animals were culled at each timepoint for tissue analysis. Tissue analysis: Optic nerves were resin embedded, sectioned (1µm) and stained with toluidine blue for myelin analysis, or cryosectioned for immunofluorescence, and retinas were flat-mounted for ganglion cell counts. Results : 3 weeks after injection with 15ng/kg DT, optic nerves showed colocalisation of activated caspase 3 & olig2, consistent with the apoptosis of oligodendroglia. Gliosis and axonal degeneration were evident.