Angiotensin-converting enzyme 2 (ACE2) was identified as the main host cell receptor for the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its subsequent infection. In some coronavirus disease 2019 (COVID-19) patients, it has been reported that the nervous tissues and the eyes were also affected. However, evidence supporting that the retina is a target tissue for SARS-CoV-2 infection is still lacking. This present study aimed to investigate whether ACE2 expression plays a role in human retinal neurons during SARS-CoV-2 infection. Human induced pluripotent stem cell (hiPSC)-derived retinal organoids and monolayer cultures derived from dissociated retinal organoids were generated. To validate the potential entry of SARS-CoV-2 infection in the retina, we showed that hiPSC-derived retinal organoids and monolayer cultures endogenously express ACE2 and transmembrane serine protease 2 (TMPRSS2) on the mRNA level. Immunofluorescence staining confirmed the protein expression of ACE2 and TMPRSS2 in retinal organoids and monolayer cultures. Furthermore, using the SARS-CoV-2 pseudovirus spike protein with GFP expression system, we found that retinal organoids and monolayer cultures can potentially be infected by the SARS-CoV-2 pseudovirus. Collectively, our findings highlighted the potential of iPSC-derived retinal organoids as the models for ACE2 receptor-based SARS-CoV-2 infection.
【저자키워드】 COVID-19, SARS-CoV-2, ACE2, Spike protein, induced pluripotent stem cells, SARS-CoV-2 pseudovirus, organoids, TMPRSS2, 【초록키워드】 coronavirus disease, Coronavirus disease 2019, coronavirus, SARS-COV-2 infection, Human, Infection, ACE2 receptor, severe acute respiratory syndrome Coronavirus, angiotensin-converting enzyme 2, Spike protein, Culture, pseudovirus, SARS-CoV-2 pseudovirus, eye, Retina, respiratory, transmembrane serine protease 2, ACE2 expression, expression, patients, Angiotensin-converting enzyme, Evidence, angiotensin, Neuron, stem cell, in some, host cell, monolayer cultures, target tissue, nervous tissues, acute respiratory syndrome, Serine, acute respiratory syndrome coronavirus, tissue, acute respiratory syndrome coronavirus 2, enzyme, transmembrane serine protease, protein expression, host cell receptor, cultures, eyes, Express, immunofluorescence staining, mRNA level, GFP, Cell, affected, reported, subsequent, entry of SARS-CoV-2, retinal organoid, the SARS-CoV-2, 【제목키워드】 Organoid, induced, endogenous, STEM, Retinal,