Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 3, Pages -Publisher
MDPI
DOI: 10.3390/ijms22031320
Keywords
COVID-19; SARS-CoV-2; SARS-CoV-2 pseudovirus; spike protein; ACE2; organoids; induced pluripotent stem cells
Funding
- Ministry of Science and Technology [MOST 107-2314-B-075033-MY3, MOST 109-2923-B-075-001-MY2, MOST 109-2314-B-075-029, MOST 109-2320-B-075-008]
- Taipei Veterans General Hospital [V109C-126, V110C-128, V110C-185, V110B-020, V110B-037]
- Yen Tjing Ling Medical Foundation, Taiwan [CI-109-26]
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This study identified the expression of ACE2 and TMPRSS2 in human induced pluripotent stem cell (hiPSC)-derived retinal organoids, and demonstrated the potential infection of SARS-CoV-2 pseudovirus in retinal organoids and monolayer cultures. These findings highlight the potential of iPSC-derived retinal organoids as models for ACE2 receptor-based SARS-CoV-2 infection.
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.
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