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Global Translational Medicine Ocular changes in Alzheimer’s disease

between retinal neuronal degeneration and the brain. An 3.4.2. Macula
in vivo study using 3×Tg AD mice revealed a correlation Another region of interest for ocular changes in AD is the
between retinal thinning and reduced gray matter in the macula, which is the thin, light-sensitive region found in
visual cortex assessed using MRI. Similarly, Bevan et al. the center of the retina. It contains the bodies of retinal
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5,17
found a correlation between RGC dendritic loss and a and glial cells, allowing it to be an estimated measure of
reduction in hippocampal dendritic spines in multiple neuronal loss. There has been research using OCT on the
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transgenic AD mouse models. 48 macula to examine volume and thickness. A decreased
5,45
The correlation between RNFL thickness and cognitive macular thickness and volume was found in AD patients
function in humans was also studied. For each micron compared to the control group. 5,45,53 Interestingly, the
increase in RNFL thickness, there was an associated 0.3 macular thickness was increased in the aMCI group
increase in the mini-mental state examination (MMSE) relative to both the control and AD groups. Another study
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score. A 2016 study also found that RNFL thickness found no significant difference in the macular volume
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decreased as AD symptom severity increased. However, between the MCI and AD groups. These results contrast
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there is also contradictory evidence with no significant the association observed with increased RNFL thinning
difference in RNFL thickness identified between the in MCI patients. This difference could be due to the
MCI and AD group. This conflicting finding could stem activation and swelling of RGC and glial cells caused by
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from the study’s exclusion of participants with severe AD, early degeneration at the MCI stage. One piece of evidence
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thereby rendering the MCI and AD groups more similar supporting increased macular volume and thickness is the
compared to other studies. 49 presence of swollen neurons as a pathological feature of
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Age-matched controls were used as a comparator in AD. Furthermore, hypertrophy of Müller glial cells has
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studies investigating RNFL thinning in AD. A greater been detected in early retinal neurodegeneration. Thus,
5,43
reduction was noted in aMCI and AD groups, implying swelling of the neuronal and glial cells caused by early
that RNFL thinning to the extent it was observed was not retinal degeneration may cause increased macular volume
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a normal process of aging. Furthermore, Ascaso et al. and thickness in MCI patients. Nevertheless, more
5,43
found a decrease in RNFL thickness in all quadrants with research should be performed to explore the mechanism
a more pronounced reduction in the superior and inferior underlying macular thickening in MCI patients.
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quadrants of the retina. More extensive thinning of the 3.5. Retinal vasculature
RNFL in the superior and inferior quadrants has been
detected in other studies. 45,49,50 although Berisha et al. only 3.5.1. Similarities between brain and retinal
found significant RNFL thinning in the superior quadrant, vasculature
which may result from the small sample size of nine AD One of the similarities between the retina and the brain
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patients. It has been proposed that more extensive RNFL is the vasculature. Both have non-anastomotic end
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thinning in the superior quadrant could be due to the arteries, and the retina has a blood–retina barrier (BRB)
greater Aβ burden identified in this region. 22,31,33 that resembles the blood–brain barrier (BBB). These
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Moreover, longitudinal studies utilizing OCT tests have blood barriers are similar structurally in terms of the
examined the development of cognitive changes based presence of endothelial cells with tight junctions in
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on a thinner RNFL at baseline. A 2019 study examined between that create a mechanical barrier. In addition,
APP/PS1 mice over 12 months and noticed thinning of both barriers have pericytes containing α-smooth muscle
the nerve fiber layer before the development of AD-like actin surrounding the endothelial capillary crucial for
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cognitive impairment. A study on human participants maintaining the permeability of the blood–tissue barrier.
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explored the relationship between RNFL thickness and They are also similar functionally in terms of high oxygen
the risk of developing AD. Between 2007 and 2012, content in the blood and the ability to self-regulate blood
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OCT was performed on participants over the age of flow by controlling vascular resistance through the activity
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45 years identified as free from stroke, Parkinson’s disease, of smooth muscles and pericytes. In AD, the function of
multiple sclerosis, and certain ocular disorders. After the BBB involves the clearance of Aβ peptides to reduce
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OCT testing, participants were followed until 2015 to accumulation in the brain, and given their similarity, the
assess dementia development. Those who had a thinner BRB could also facilitate Aβ removal.
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RNFL at baseline had a significantly increased risk of Extensive research has been performed examining
developing AD with a hazard ratio of 1.43. This suggests the cerebral vascular changes in AD. Cerebral amyloid
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thinning of the RNFL can serve as an early biomarker for angiopathy characterized by the deposition of Aβ on
the development of AD. the basement membrane of the blood vessels is present
Volume 3 Issue 3 (2024) 7 doi: 10.36922/gtm.4094