Coviretinopathy: COVID-19-induced VEGF-dependent retinopathy
COVID-19 has been associated with high prevalences of retinal diseases in humans. However, cellular and molecular mechanisms that underly the COVID-19-associated retinopathy remains unknown. Here, we deployed a mouse COVID-19 model to investigate the causative link between SARS-CoV-2 infection and retinopathy development. Our data showed that COVID-19-induced pulmonary hypoxia triggered systemic hypoxia and markedly augmented VEGF expression levels in the retina and plasma. High VEGF levels altered vascular structures and functions in the retina, resulting in neovascularization, vascular disorganization and increased leakiness. We deployed a new terminology of coviretinopathy to accurately describe these COVID-19-induced pathological changes in the retina. Consequently, blocking VEGF by a specific neutralizing antibody (VEGF blockade) completely ablated the COVID-19-associated vascular changes in the retina. Together, these findings provide new mechanistic insights into the COVID-19-associated retinopathy and propose a new therapeutic paradigm for effective treatment of coviretinopathy. Overall design: Mouse lung and retinal tissues were dissociated into single-cell suspensions and processed by CapitalBio Technology (Beijing, China) using the 10x Genomics Chromium platform with the Single Cell 3' Library Kit v2. Libraries were sequenced on an Illumina NovaSeq 6000 (paired-end 150 bp, >100,000 reads/cell). The data were processed with Cell Ranger, and downstream analysis, including clustering (Seurat), pseudotime trajectory (Monocle 2), and functional enrichment (DAVID), was performed using standard pipelines.