Abstract
Accumulation of amyloid-beta (Aβ) peptides is regarded as the hallmark of neurodegenerative alterations in the brain of Alzheimer’s disease (AD) patients. In the eye, accumulation of Aβ peptides has also been suggested to be a trigger of retinal neurodegenerative mechanisms. Some pathological aspects associated with Aβ levels in the brain are synaptic dysfunction, neurochemical remodeling and glial activation, but these changes have not been established in the retina of animals with Aβ accumulation. We have employed the Octodon degus in which Aβ peptides accumulated in the brain and retina as a function of age. This current study investigated microglial morphology, expression of PSD95, synaptophysin, Iba-1 and choline acetyltransferase (ChAT) in the retina of juvenile, young and adult degus using immunolabeling methods. Neurotransmitters glutamate and gamma-aminobutyric acid (GABA) were detected using immunogold labeling and glutamate receptor subunits were quantified using Western blotting. There was an age-related increase in presynaptic and a decrease in post-synaptic retinal proteins in the retinal plexiform layers. Immunolabeling showed changes in microglial morphology characteristic of intermediate stages of activation around the optic nerve head (ONH) and decreasing activation toward the peripheral retina. Neurotransmitter expression pattern changed at juvenile ages but was similar in adults. Collectively, the results suggest that microglial activation, synaptic remodeling and neurotransmitter changes may be consequent to, or parallel to Aβ peptide and phosphorylated tau accumulation in the retina.
Highlights
Elevated levels of amyloid beta (Aβ) proteins and the associated cell damage have been described in the aging eye and opened up the possibility of Aβ being a key constituent of age-related ocular pathologies (Hinton et al, 1986; Dutescu et al, 2009; Koronyo-Hamaoui et al, 2011; Koronyo et al, 2017)
Aβ accumulation in the retina is a sign of amyloidosis associated neurodegeneration (Koronyo-Hamaoui et al, 2011), and is observed in diabetes (Bitel et al, 2012)
In neurodegenerative diseases with Aβ accumulation in the retina, such as in Alzheimer’s disease–like (AD) (Blanks et al, 1996a,b) peptide accumulation is seen in the retina before the brain (Chang et al, 2014, 2015; Du et al, 2015)
Summary
Elevated levels of amyloid beta (Aβ) proteins and the associated cell damage have been described in the aging eye and opened up the possibility of Aβ being a key constituent of age-related ocular pathologies (Hinton et al, 1986; Dutescu et al, 2009; Koronyo-Hamaoui et al, 2011; Koronyo et al, 2017). Several investigations using the Octodon degus (degus) have confirmed a role for Aβ peptides in diseases, including increased Aβ peptides and phosphorylated tau levels in the adult retina (Acosta et al, 2014; Du et al, 2015) or altered retinal structure with age (Szabadfi et al, 2015). Inbreeding of laboratory-bred degus may display different co-morbidities and exposure to stress compared to wild-captured bred degus (Palacios and Lee, 2013; Ibanez et al, 2018). We conducted this investigation using tissues from a colony of degus that had occurrence of Aβ peptides and phosphorylated tau in adult animals, and animals that had behavioral testing to infer their neurological status
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