Single-cell transcriptomic atlas reveals tissue architecture and deciphers pathological reprogramming during retinal ischemia in Macaca fascicularis

Acute retinal arterial ischemia diseases (ARAIDs) are ocular emergencies that require immediate intervention within a restricted therapeutic window to prevent blindness. Howbeit, the underlying molecular mechanisms contributing to the pathogenesis of ARAIDs remain enigmatic. Herein, this study aims to present the single cell RNA sequencing (scRNA-seq) atlas of ischemic alterations in the primate retina as a preliminary endeavor in understanding the molecular complexities of ARAIDs. In our study, it was determined that rods experienced a significant metabolic reprogramming during retina ischemia, resulting in compromised mitochondrial functions. Furthermore, we observed a noteworthy transcriptional alteration in the activation of microglia induced by ischemia. The targeted correction of the proinflammatory cytokine CXCL8 effectively suppresses microglia M1 polarization in retinal ischemia, ultimately reducing the pro-inflammatory transformation. In addition, our study has observed the apoptotic inclination of endothelial cells and the heightened interaction with microglia, which signifies the influence of microglia in disrupting the blood barrier during the initial phase. In conclusion, our research has successfully identified and described the pathological alterations occurring in several significant cell types during a short period of ischemia. These observations provide valuable insights for ameliorating retinal damage and promoting the restoration of vision. The ophthalmic artery of one macaca fascicularis was ligated for six hours, another macaca fascicularis underwent the same operation without ligation. The retinas of two macaca fascicularis were isolated immediately and digested into single cell suspension for scRNS-seq.