A new study by researchers from Max Planck Institute for Molecular Biomedicine has discovered that the SARS-CoV-2 coronavirus is able to infect and replicate in the photoreceptor and also retinal ganglion cells of human retinal organoids.
The study findings were published on a preprint server and are currently being peer reviewed.
https://www.biorxiv.org/content/10.1101/2021.10.09.463766v1
The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global pandemic that is responsible for millions of fatalities. While mild-to-severe respiratory symptoms are most commonly associated with the disease (Huang et al., 2020), neurological (Asadi-Pooya and Simani, 2020; Mao et al., 2020) and ocular (Wu et al., 2020) symptoms have also been described in patients.
Growing evidence suggests retinal involvement in some cases of COVID-19.
Different reports identified SARS-CoV-2 RNA in retinal and optic nerve biopsies taken from deceased COVID- 19 patients (Casagrande et al., 2020; Casagrande et al., 2021), while different retinal anomalies were also identified in patients (Burgos-Blasco et al., 2020; Conrady et al., 2021; Marinho et al., 2020; Pereira et al., 2020; Rodriguez-Rodriguez et al., 2021; Virgo and Mohamed, 2020). Yet, retinal involvement in COVID-19 remains a controversial topic, as other studies were not able to detect retinal pathologies in patients (Pirraglia et al., 2020).
Furthermore, one study reported failure to isolate virus from SARS-CoV-2 RNA–positive retinal biopsies and an inability to detect any SARS-CoV-2 spike protein from those biopsies by immunohistochemical analysis, leading investigators to suggest that SARS-CoV-2 can infect but not actively replicate in retinal cells (Casagrande et al., 2021).
It also remains unclear which retinal structures are infected by SARS-CoV-2 and whether the retinal anomalies reported are due to retinal infection or systemic organ dysfunction (Casagrande et al., 2020; de Figueiredo et al., 2020).
Organoids are three-dimensional, tissue cultures that resemble specific organs in their morphology, cell-type composition, or function. Different research groups have used organoids generated from human stem cells to study the infection of SARS-CoV-2 in the context of different organs (Lamers et al., 2020; Monteil et al., 2020; Pellegrini et al., 2020; Ramani et al., 2020; Zhang et al., 2020).
Such studies have demonstrated that SARS-CoV-2 can infect neurons and neural progenitors (Ramani et al., 2020; Zhang et al., 2020). Retinal organoids are among the most physiologically accurate neural organoid models, as they contain all the major retinal cell types, follow a developmental trajectory similar to that of the human retina in vivo, and are correctly organized in a typical layered structure (Achberger et al., 2019; Nakano et al., 2012; Zhong et al., 2014).
Here we use retinal organoids to show that SARS-CoV-2 can infect retinal cells, mainly retinal ganglion cells (RGCs) but also photoreceptors, as well as replicate in them.
