Abstract
BackgroundIt has been claimed that the retina can be used as a window to study brain disorders. However, concerning Alzheimer’s disease (AD), it still remains controversial whether changes occurring in the brain and retina are associated. We aim to understand when changes start appearing in the retina and brain, how changes progress, and if they are correlated.MethodsWe carried out a unique longitudinal study, at 4, 8, 12, and 16 months of age, in a triple transgenic mouse model of AD (3×Tg-AD), which mimics pathological and neurobehavioral features of AD, as we have already shown. Retinal structure and physiology were evaluated in vivo using optical coherence tomography and electroretinography. Brain visual cortex structure was evaluated in vivo using magnetic resonance imaging.ResultsThe retinal thickness of 3×Tg-AD decreased, at all time points, except for the outer nuclear layer, where the opposite alteration was observed. Amplitudes in scotopic and photopic responses were increased throughout the study. Similarly, higher amplitude and lower phase values were observed in the photopic flicker response. No differences were found in the activity of retinal ganglion cells. Visual cortex gray matter volume was significantly reduced.ConclusionsOur results show that this animal model shows similar neural changes in the retina and brain visual cortex, i.e., retinal and brain thinning. Moreover, since similar changes occur in the retina and brain visual cortex, these observations support the possibility of using the eye as an additional tool (noninvasive) for early AD diagnosis and therapeutic monitoring.
Highlights
It has been claimed that the retina can be used as a window to study brain disorders
Throughout the study, we observed a significant thinning of ganglion cell layer (GCL)+inner plexiform layer (IPL) (F (2.6, 85.7) = 3.4, p < 0.05) and inner nuclear layer (INL)+outer plexiform layer (OPL) (F (2.2, 72.5) = 19.0, p < 0.001), whereas no time effect was observed on the inner segments (IS)+outer segments (OS) layer thickness (F (2.5, 82.8) = 0.73, p = 0.510)
The thickness of each retinal layer was consistently significantly lower in Triple transgenic mouse model of Alzheimer’s disease (3×Tg-Alzheimer’s disease (AD)) mice compared to Wild type (WT) mice (GCL+IPL, F (1, 33) = 121.8, p < 0.001; INL+OPL, F (1, 33) = 22.7, p < 0.001; IS+OS layer, F (1, 33) = 105.1, p < 0.001) (Fig. 1)
Summary
It has been claimed that the retina can be used as a window to study brain disorders. Concerning Alzheimer’s disease (AD), it still remains controversial whether changes occurring in the brain and retina are associated. Visual alterations have been detected in AD patients, and those alterations can be associated with structural and functional changes in the retina [7,8,9]. Retinal nerve fiber layer (RNFL) thickness reduction has been observed in AD patients [8, 21,22,23,24,25]. Further studies in AD patients showed the reduction of ganglion cell layer (GCL) [18, 30, 31] and inner plexiform layer (IPL) thickness [32,33,34], as well as cortical atrophy, namely the decrease in the volume of visual cortex [35, 36]. The existence of Aβ plaques in the retina was reported in several AD animals models [14], and in both post-mortem retinas of advanced and early stage AD patients [37, 38] and, using curcumin-based fundus imaging, in AD patients [39]
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