Angiotensin Converting Enzyme 2 (ACE2) Expression in the Aged Brain and Visual System
2021
Multiple lines of evidence currently indicate that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
gains entry into human host cells via a high-affinity interaction with the angiotensin-converting enzyme 2 (ACE2)
transmembrane receptor. Research has further shown the widespread expression of the ACE2 receptor on the surface
of many different immune, non-immune and neural host cell types, and that SARS-CoV-2 has the remarkable
capability to attack many different types of human-host cells simultaneously. One principal neuroanatomical region
for high ACE2 expression patterns occurs in the brainstem, an area of the brain containing regulatory centers for
respiration, and this may in part explain the predisposition of many COVID-19 patients to respiratory distress. Early
studies also indicated extensive ACE2 expression in the whole eye and the brain’s visual circuitry in aged humans. In
this study we analyzed ACE2 receptor expression at the mRNA and protein level in multiple cell types involved in
human vision, including cell types of the external eye and several deep brain regions known to be involved in the
processing of visual signals. Here we provide evidence: (i) that many different optical and neural cell types of the
human visual system provide receptors essential for SARS-CoV-2 invasion; (ii) of the remarkable ubiquity of ACE2
presence in cells of the eye and anatomical regions of the brain involved in visual signal processing; (iii) that ACE2
receptor expression in different ocular cell types and visual processing centers of the brain provide multiple compartments for SARS-CoV-2 infiltration; and (iv) of a gradient of increasing ACE2 expression from the anterior surface of the eye to the visual signal processing areas of the occipital lobe and the primary visual neocortex. A
gradient of ACE2 expression from the eye surface to the occipital lobe may provide the SARS-CoV-2 virus a novel
pathway from the outer eye into deeper anatomical regions of the brain involved in vision. These findings may
explain, in part, the many recently reported neuro-ophthalmic manifestations of SARS-CoV-2 infection in COVID-19 affected patients.
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