tetano
Editor, Senior Moderator
Cell Biosci
. 2025 Apr 11;15(1):43.
doi: 10.1186/s13578-025-01383-0. The influence of SARS-CoV-2 spike protein exposure on retinal development in the human retinal organoids
Jing Gong[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Lingling Ge[SUP] #[/SUP][SUP] 1 2 [/SUP], Yuxiao Zeng[SUP] 1 2 [/SUP], Cao Yang[SUP] 1 2 [/SUP], Yushan Luo[SUP] 1 2 [/SUP], Jiahui Kang[SUP] 1 2 [/SUP], Ting Zou[SUP] 4 5 6 [/SUP], Haiwei Xu[SUP] 7 8 [/SUP]
Affiliations
Background: Pregnant women are considered a high-risk population for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as the virus can infect the placenta and embryos. Recently, SARS-CoV-2 has been widely reported to cause retinal pathological changes and to infect the embryonic retina. The infection of host cells by SARS-CoV-2 is primarily mediated through spike (S) protein, which also plays a crucial role in the pathogenesis of SARS-CoV-2. However, it remains poorly understood how the S protein of SARS-CoV-2 affects retinal development, and the underlying mechanism has not yet been clarified.
Methods: We used human embryonic stem cell-derived retinal organoids (hEROs) as a model to study the effect of S protein exposure at different stages of retinal development. hEROs were treated with 2 μg/mL of S protein on days 90 and 280. Immunofluorescence staining, RNA sequencing, and RT-PCR were performed to assess the influence of S protein exposure on retinal development at both early and late stages.
Results: The results showed that ACE2 and TMPRSS2, the receptors facilitating SARS-CoV-2 entry into host cells, were expressed in hEROs. Exposure to the S protein induced an inflammatory response in both the early and late stages of retinal development in the hEROs. Additionally, RNA sequencing indicated that early exposure of the S protein to hEROs affected nuclear components and lipid metabolism, while late-stages exposure resulted in changes to cell membrane components and the extracellular matrix.
Conclusion: This work highlights the differential effects of SARS-CoV-2 S protein exposure on retinal development at both early and late stages, providing insights into the cellular and molecular mechanisms underlying SARS-CoV-2-induced developmental impairments in the human retina.
Keywords: Retinal development; Retinal organoid; SARS-CoV-2; Spike protein.
. 2025 Apr 11;15(1):43.
doi: 10.1186/s13578-025-01383-0. The influence of SARS-CoV-2 spike protein exposure on retinal development in the human retinal organoids
Jing Gong[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Lingling Ge[SUP] #[/SUP][SUP] 1 2 [/SUP], Yuxiao Zeng[SUP] 1 2 [/SUP], Cao Yang[SUP] 1 2 [/SUP], Yushan Luo[SUP] 1 2 [/SUP], Jiahui Kang[SUP] 1 2 [/SUP], Ting Zou[SUP] 4 5 6 [/SUP], Haiwei Xu[SUP] 7 8 [/SUP]
Affiliations
- PMID: 40217547
- PMCID: PMC11987193
- DOI: 10.1186/s13578-025-01383-0
Background: Pregnant women are considered a high-risk population for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as the virus can infect the placenta and embryos. Recently, SARS-CoV-2 has been widely reported to cause retinal pathological changes and to infect the embryonic retina. The infection of host cells by SARS-CoV-2 is primarily mediated through spike (S) protein, which also plays a crucial role in the pathogenesis of SARS-CoV-2. However, it remains poorly understood how the S protein of SARS-CoV-2 affects retinal development, and the underlying mechanism has not yet been clarified.
Methods: We used human embryonic stem cell-derived retinal organoids (hEROs) as a model to study the effect of S protein exposure at different stages of retinal development. hEROs were treated with 2 μg/mL of S protein on days 90 and 280. Immunofluorescence staining, RNA sequencing, and RT-PCR were performed to assess the influence of S protein exposure on retinal development at both early and late stages.
Results: The results showed that ACE2 and TMPRSS2, the receptors facilitating SARS-CoV-2 entry into host cells, were expressed in hEROs. Exposure to the S protein induced an inflammatory response in both the early and late stages of retinal development in the hEROs. Additionally, RNA sequencing indicated that early exposure of the S protein to hEROs affected nuclear components and lipid metabolism, while late-stages exposure resulted in changes to cell membrane components and the extracellular matrix.
Conclusion: This work highlights the differential effects of SARS-CoV-2 S protein exposure on retinal development at both early and late stages, providing insights into the cellular and molecular mechanisms underlying SARS-CoV-2-induced developmental impairments in the human retina.
Keywords: Retinal development; Retinal organoid; SARS-CoV-2; Spike protein.