Can SARS-CoV-2 infect the eye? An overview of the receptor status in ocular tissue
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Sven Schnichels · Jens Martin Rohrbach · Tarek Bayyoud · Sebastian Thaler · Focke Ziemssen · José Hurst Universitäts-Augenklinik Tübingen, Tübingen, Germany
Can SARS-CoV-2 infect the eye? An overview of the receptor status in ocular tissue In recent decades, a number of coronaviruses have crossed the species barrier to humans and caused outbreaks of severe and often fatal respiratory diseases. The transmission of viruses from animals to humans is referred to as zoonosis and has mostly occurred at Asian animal markets, where large numbers of people and animals can be found together in a small area. In addition to the current SARS-CoV-2 virus, other known viruses crossing the species barrier include SARS-CoV and MERSCoV. These viruses all belong to the betacoronaviruses [1]. Coronaviruses encode a surface glycoprotein—a socalled spike protein—that binds to the host cell receptor and mediates virus entry [2]. SARS-CoV-2 uses the human angiotensin-converting enzyme-2 (ACE2) receptor to enter cells [3–7]. Receptor interaction with the target cell is the main component of cross-species transmission, particularly in betacoronaviruses. In these viruses, a single region of the spike protein called the receptor-binding domain (RDB) mediates interaction with the host cell receptor. Following receptor binding, a target cell protease cleaves the spike that releases the spike fusion peptide, thereby facilitating virus entry [1, 8–10]. In addition to ACE2 for SARS-CoV, the known host receptors for betacoronaviruses include dipeptidylpeptidase-4 (DPP4) for MERS-CoV [11, 12], whereby SARSCoV-2 has a higher affinity for ACE2 The German version of this article can be found under https://doi.org/10.1007/s00347020-01160-z.
than SARS-CoV [13]. This effect is due to several changes in the gene and thus in the amino acid sequence of the spike protein compared to that of SARS-CoV [14]. The mammalian serine protease TMPRSS2 and the protease furin have been identified as relevant proteases for the interaction of the spike protein with ACE2 [15–17]. The ACE2 receptor is part of the renin–angiotensin system (RAS). This system plays a crucial role in the regulation of blood pressure as well as fluid and electrolyte homeostasis. It comprises dozens of angiotensin peptides and peptidases and at least six receptors, including ACE2 [18].
Contradictions in the publications First of all, it must be said that until the outbreak of the current coronavirus pandemic, there was only scant evidence on expression of the receptor and the involved proteases in the eye. Recently, the number of publications has grown. Some of these publications are—at first glance—contradictory. Without discussing each individual publication here, there are various reasons for this: Firstly, the RNA and protein expression of a receptor very often differs, as could be determined in other, better-investigated ACE2-positive tissues (https://www.proteinatlas. org/ENSG00000130234-ACE2/tissue). Unfortunately, since that particular review is not up to date, no findings for the eye can be fo
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