ACE2 EXPRESSION LEVELS IN THE BRAIN AND EYE

To Whom It May Concern: As evidenced by multiple research studies, the SARS-CoV2 virus employs the angiotensin converting enzyme 2 (ACE 2) cell surface receptor to gain entry into host cells; this is a necessary first step for SARS-CoV2 invasion, replication and multiplication within human host cells; To ascertain what types of cells and tissues might be the most susceptible to SARS-CoV2 invasion, we have quantified ACE2 expression (at the mRNA level and some at the protein level) in about ~100 different cell types and tissues of the human brain, eye and central nervous system (CNS); Some of the data appear in this recent report from our laboratory: Lukiw WJ, Pogue A, Hill JM. SARS-CoV-2 Infectivity and Neurological Targets in the Brain. Cell Mol Neurobiol. 2020 Aug 25:1–8. doi: 10.1007/s10571-020-00947-7. Epub ahead of print. PMID: 32840758; PMCID: PMC7445393. and in the figures and tables associated with this publication; [appended; please also refer to the Abstract below] Another very recent report has been submitted to the Journal Cellular and Molecular Neurobiology (15 November 2020) for peer-review and is tentatively entitled: ‘ACE2 receptor expression in the human visual system” These data should be of sincere interest to SARS-CoV2 and COVID-19 researchers and expand our understanding of potential cell and tissue targets bearing the ACE2 receptor for SARS-CoV2 invasion and infectivity, and suggest possible visual and neurological routes for SARS-CoV2-cellular entry during the COVID-19 pandemic. Yours truly, Walter J. Lukiw BS, MS, PhD, Professor of Neuroscience and Ophthalmology, Bollinger Professor of Alzheimer’s disease, LSU Neuroscience Center and Department of Ophthalmology, Louisiana State University Health Sciences Center, 2020 Gravier Street, Room 904, New Orleans LA 70112 USA TEL [phone]; EMAIL [e-mail] ================================================================================ Paper of interest: Lukiw WJ, Pogue A, Hill JM. SARS-CoV-2 Infectivity and Neurological Targets in the Brain. Cell Mol Neurobiol. 2020 Aug 25:1–8. doi: 10.1007/s10571-020-00947-7. Epub ahead of print. PMID: 32840758; PMCID: PMC7445393. Abstract The gateway for invasion by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into human host cells is via the angiotensin-converting enzyme 2 (ACE2) transmembrane receptor expressed in multiple immune and nonimmune cell types. SARS-CoV-2, that causes coronavirus disease 2019 (COVID-19; CoV-19) has the unusual capacity to attack many different types of human host cells simultaneously via novel clathrin- and caveolae-independent endocytic pathways, becoming injurious to diverse cells, tissues and organ systems and exploiting any immune weakness in the host. The elicitation of this multipronged attack explains in part the severity and extensive variety of signs and symptoms observed in CoV-19 patients. To further our understanding of the mechanism and pathways of SARS-CoV-2 infection and susceptibility of specific cell- and tissue-types and organ systems to SARS-CoV-2 attack in this communication we analyzed ACE2 expression in 85 human tissues including 21 different brain regions, 7 fetal tissues and 8 controls. Besides strong ACE2 expression in respiratory, digestive, renal-excretory and reproductive cells, high ACE2 expression was also found in the amygdala, cerebral cortex and brainstem. The highest ACE2 expression level was found in the pons and medulla oblongata in the human brainstem, containing the medullary respiratory centers of the brain, and may in part explain the susceptibility of many CoV-19 patients to severe respiratory distress. Keywords: Alzheimer’s disease; Angiotensin-converting enzyme 2 (ACE2) receptor; COVID-19; CoV-19; Coronavirus; Hartnup's disease; SARS-CoV-2; miRNA-5197; microRNA; single stranded RNA (ssRNA). ================================================================================