SIRT2 inhibition attenuates the vasculopathy and vision impairment via Akt signaling in retinopathy of prematurity

Despite decades of researches, the underlying mechanism of retinopathy of prematurity (ROP) remains unclear. The role of Sirt2, which is involved in both angiogenesis and inflammation, both pivotal in ROP, was investigated in an animal model of ROP known as oxygen-induced retinopathy (OIR). Our study found that Sirt2 was overexpressed and colocalized with microglia in OIR. Furthermore, it demonstrated that the level of Sirt2 was upregulated in hypoxia microglia BV-2 in vitro. Subsequently, our results elucidated that administration of the Sirt2 antagonist AGK2 attenuated the avascular and neovascular area and downregulated the expression of IGF1. The phosphorylation of Akt and the expression of IGF-1 were upregulated in hypoxia BV-2 and conditional media collected from BV-2 under hypoxia promoted the migration and tube formation of retinal capillary endothelial cells, which were suppressed with AGK2. Notably, our findings are the first to demonstrate the deleterious role of Sirt2 in ROP, as Sirt2 inhibition led to the downregulation of Akt/IGF-1 and ameliorated vasculopathy, ultimately improving visual function. These results suggest that Sirt2 may be a promising therapeutic target for ROP.

Automated summary

Despite extensive research, the exact mechanism of retinopathy of prematurity (ROP) is still unclear. In this study, the role of Sirt2, involved in both angiogenesis and inflammation, was investigated in a ROP animal model. The study found that Sirt2 was overexpressed and co-located with microglia in the model. Additionally, the study demonstrated that Sirt2 levels were upregulated in hypoxic microglia BV-2 in vitro.