June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Evaluation of neurovascular changes in retinal sublayers reveals differentiable retinal degeneration in Alzheimer's disease as compared natural aging
Author Affiliations & Notes
  • Hossein Khanamiri Nazari Khanamiri
    Ophthalmology and Visual Neuroscience, University of Minnesota Medical School Twin Cities, Minneapolis, Minnesota, United States
  • Mauro Montalbano
    The University of Texas Medical Branch at Galveston, Galveston, Texas, United States
  • Wenbo Zhang
    The University of Texas Medical Branch at Galveston, Galveston, Texas, United States
  • Massoud Motamedi
    The University of Texas Medical Branch at Galveston, Galveston, Texas, United States
  • Footnotes
    Commercial Relationships   Hossein Nazari Khanamiri None; Mauro Montalbano None; Wenbo Zhang None; Massoud Motamedi None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 4123 – F0360. doi:
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      Hossein Khanamiri Nazari Khanamiri, Mauro Montalbano, Wenbo Zhang, Massoud Motamedi; Evaluation of neurovascular changes in retinal sublayers reveals differentiable retinal degeneration in Alzheimer's disease as compared natural aging. Invest. Ophthalmol. Vis. Sci. 2022;63(7):4123 – F0360.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : The retina is a visible extension of the brain that may reflect brain neurodegeneration caused by Alzheimer's disease (AD) and natural senescence. The spatial distributions of neurons, glial, and vasculature, which may be afflicted at different stages of a neurodegenerative process, vary in retinal sublayers. Thus, we aimed to characterize and differentiate the spatial and temporal distribution of AD- versus senescence-induced neuronal and vascular changes of the retina based on immunohistochemistry and optical coherence tomography (OCT) studies in the triple transgenic mouse model of AD (3xTg-AD).

Methods : The retina’s superficial (SVP), middle (MVP), and deep (DVP) vascular plexuses were studied in young (2 months old-M) to middle-aged (14M) and old (18-20M) 3xTg-AD and C57bl/6j mice. Amyloid-β (Aβ) and phosphorylated-tau (ptau) deposition were characterized in retinal and brain samples from 4M, 8M, and 12M animals. Retinal sublayer thicknesses were analyzed in annular OCT scans and retinal ganglion cells (RGCs) were quantified in retina flat-mounts in 2M to 12M transgenic and control mice.

Results : Progressive deposition of Aβ and ptau was detected in the retina (4M) before the brain (8M). Vascular attenuation and RGC loss occurred with AD pathology and natural aging; however, RGC loss was more significant in 8M and 12M 3xTg-AD compared to old controls (p=0.0426 and p=0.0002, respectively). SVP and DVP, but not MVP, attenuation differentiated old 3xTg-AD from old controls (P<0.05). The retinal nerve fiber layer (RNFL), but not ganglion cell layer (GCL), thickness decreased (linear regression, p=0.0002) as 3xTg-AD mice aged.

Conclusions : In our animal models, the retina manifests AD pathologies before the brain. Various degrees of AD-induced neurovascular coupling dysfunction within the retina layers can be monitored and quantified as biomarkers of AD progression using noninvasive OCT and OCTA approaches. Retinal neurovascular (NV) biomarkers may differentiate AD-neurodegeneration from neurodegeneration caused by natural aging. More specifically, GCL thickening by neuroinflammation and NV dysfunction (trophic changes) may nullify the thinning effect caused by RGC loss (atrophic changes) in AD but not in natural aging. In contrast, the hypocellular RNFL is less affected by the trophic effects of neuroinflammation and NV dysfunction.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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