Circular RNA circSNRK regulates inflammatory processes and TXNIP expression by acting as a miR-128-3p sponge in age-related macular degeneration

Age-related macular degeneration (AMD) is an ocular disease that causes visual impairment in older individuals, primarily due to degeneration of the retinal pigment epithelium (RPE). In this progressive disease, damaged RPE cells release pro-inflammatory factors into the extracellular space, leading to macrophage infiltration. However, the role of non-coding RNAs, including circular RNAs (circRNAs), in AMD remains largely unclear. This study aims to elucidate the role of circRNAs in AMD pathogenesis. By analyzing total RNA sequencing data from RPEs of the laser-induced choroidal neovascularization (CNV) model, we selected circRNA candidates for functional analysis. Transcriptome analysis of ARPE-19 cells with circSNRK knockdown revealed that circSNRK regulates the expression of cell proliferation-related genes and functions as a microRNA sponge to modulate TXNIP , the target gene of miR-128-3p. Additionally, circSNRK knockdown upregulated pro-inflammatory genes and increased macrophage migration. Using a circSNRK mutant lacking the miR-128-3p binding site, we found that the miR-128-3p/ TXNIP axis accounts for the inflammatory response but not for the change in proliferation. Finally, circSnrk inhibition enhanced inflammation-driven neovascularization in the laser-induced CNV model. Our findings suggest that circSNRK is a critical regulator of inflammation in the RPE, indicating its potential as a therapeutic target for AMD.