TY - JOUR
T1 - Retinal changes in Alzheimer's disease— integrated prospects of imaging, functional and molecular advances
AU - Gupta, Veer B.
AU - Chitranshi, Nitin
AU - Haan, Jurre den
AU - Mirzaei, Mehdi
AU - You, Yuyi
AU - Lim, Jeremiah K. H.
AU - Basavarajappa, Devaraj
AU - Godinez, Angela
AU - di Angelantonio, Silvia
AU - Sachdev, Perminder
AU - Salekdeh, Ghasem H.
AU - Bouwman, Femke
AU - Graham, Stuart
AU - Gupta, Vivek
N1 - Funding Information: More recently, there have been attempts to distinguish A? deposition in the retina using hyperspectral scanning (HSI) (Hadoux et al., 2019; More and Vince, 2015; Sharafi et al., 2019). HSI does not require extrinsic fluorophore labelling and works by acquiring and analysing adjacent wavelength spectra within a given range. This technique takes advantage of the light scattering properties of small particles in tissue, which is governed by Rayleigh scatter principle. Optical and digital processing of the sequential HS images allows non-invasive discrimination of structural and biochemical changes in the tissues. In the retina, small soluble A? oligomers are believed to contribute to an HSI signature most salient in the short visible wavelength spectrum. The proof-of-principle studies demonstrated that HSI spectral signatures from AD post-mortem brain tissue differed significantly in comparison to that acquired from normal age-matched individuals. Similar patterns of the spectral variation in wavelengths have also been observed between normal and A?1?42 peptide treated SHSY5Y cells (More and Vince, 2015). Interestingly, an analysis of retinal tissue samples from normal and AD subjects offered similar differentiating results. Total wavelength scattering in samples from AD patients was diminished, suggesting its dispersal by protein aggregation neuropathology, or associated structural alterations. Ex vivo HS imaging of retinal tissues from a mouse model at different stages of the disease, supported these observations, with significant differences observed at 4 months, which increased exponentially at 6 months of age. At 8 months, APP/PS1 mice have some A? plaque formation, and accordingly, discernible differences in HSI were further observed between the control and transgenic mice at this stage (More and Vince, 2015). Intriguingly, at 4 months of age, amyloid deposition is not evident in APP/PS1 mice brains, which suggests that the light scattering properties of small soluble A? species preserves the HSI signature even in the absence of insoluble plaques, and this property makes this approach a potentially useful tool for early detection of AD (Fig. 6).We acknowledge funding support from National Health and Medical Research Council (NHMRC) of Australia (1136602, 1139560), Perpetual Hilcrest, Ophthalmic Research Institute of Australia (ORIA) and Macquarie University, NSW, Australia. SDA acknowledges the funding support from the CrestOptics-IIT JointLab for Advanced Microscopy, Italy. Funding Information: We acknowledge funding support from National Health and Medical Research Council (NHMRC) of Australia (1136602, 1139560), Perpetual Hilcrest , Ophthalmic Research Institute of Australia (ORIA) and Macquarie University, NSW, Australia . SDA acknowledges the funding support from the CrestOptics-IIT JointLab for Advanced Microscopy, Italy. Publisher Copyright: © 2020 Elsevier Ltd
PY - 2021/5
Y1 - 2021/5
N2 - Alzheimer's Disease (AD) is a devastating neurodegenerative disorder of the brain, clinically characterised by cognitive deficits that gradually worsen over time. There is, at present, no established cure, or disease-modifying treatments for AD. As life expectancy increases globally, the number of individuals suffering from the disease is projected to increase substantially. Cumulative evidence indicates that AD neuropathological process is initiated several years, if not decades, before clinical signs are evident in patients, and diagnosis made. While several imaging, cognitive, CSF and blood-based biomarkers have been proposed for the early detection of AD; their sensitivity and specificity in the symptomatic stages is highly variable and it is difficult to justify their use in even earlier, pre-clinical stages of the disease. Research has identified potentially measurable functional, structural, metabolic and vascular changes in the retina during early stages of AD. Retina offers a distinctively accessible insight into brain pathology and current and developing ophthalmic technologies have provided us with the possibility of detecting and characterising subtle, disease-related changes. Recent human and animal model studies have further provided mechanistic insights into the biochemical pathways that are altered in the retina in disease, including amyloid and tau deposition. This information coupled with advances in molecular imaging has allowed attempts to monitor biochemical changes and protein aggregation pathology in the retina in AD. This review summarises the existing knowledge that informs our understanding of the impact of AD on the retina and highlights some of the gaps that need to be addressed. Future research will integrate molecular imaging innovation with functional and structural changes to enhance our knowledge of the AD pathophysiological mechanisms and establish the utility of monitoring retinal changes as a potential biomarker for AD.
AB - Alzheimer's Disease (AD) is a devastating neurodegenerative disorder of the brain, clinically characterised by cognitive deficits that gradually worsen over time. There is, at present, no established cure, or disease-modifying treatments for AD. As life expectancy increases globally, the number of individuals suffering from the disease is projected to increase substantially. Cumulative evidence indicates that AD neuropathological process is initiated several years, if not decades, before clinical signs are evident in patients, and diagnosis made. While several imaging, cognitive, CSF and blood-based biomarkers have been proposed for the early detection of AD; their sensitivity and specificity in the symptomatic stages is highly variable and it is difficult to justify their use in even earlier, pre-clinical stages of the disease. Research has identified potentially measurable functional, structural, metabolic and vascular changes in the retina during early stages of AD. Retina offers a distinctively accessible insight into brain pathology and current and developing ophthalmic technologies have provided us with the possibility of detecting and characterising subtle, disease-related changes. Recent human and animal model studies have further provided mechanistic insights into the biochemical pathways that are altered in the retina in disease, including amyloid and tau deposition. This information coupled with advances in molecular imaging has allowed attempts to monitor biochemical changes and protein aggregation pathology in the retina in AD. This review summarises the existing knowledge that informs our understanding of the impact of AD on the retina and highlights some of the gaps that need to be addressed. Future research will integrate molecular imaging innovation with functional and structural changes to enhance our knowledge of the AD pathophysiological mechanisms and establish the utility of monitoring retinal changes as a potential biomarker for AD.
KW - Amyloid
KW - Dementia
KW - Glaucoma
KW - Hyperspectral imaging
KW - Imaging
KW - Neuroinflammation
KW - Optic nerve
KW - Optical coherence tomography (angiography)(OCTA)
KW - Proteomics
KW - Retina
KW - Retinal ganglion cell
KW - Tau
KW - Vascular changes
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85090553221&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/32890742
U2 - https://doi.org/10.1016/j.preteyeres.2020.100899
DO - https://doi.org/10.1016/j.preteyeres.2020.100899
M3 - Review article
C2 - 32890742
SN - 1350-9462
VL - 82
JO - Progress in Retinal and Eye Research
JF - Progress in Retinal and Eye Research
M1 - 100899
ER -