Quantum molecular resonance and secretome synergistically unlocks a protective ceRNA axis in the human retinal...

The retinal pigment epithelium (RPE) contributes to retinal homeostasis in part through non-coding RNA (ncRNA) regulatory networks, and its degeneration underlies blinding diseases. How physical and paracrine regenerative stimuli affect the RPE non-coding transcriptome remains unknown. We performed RNA-seq on ARPE-19 cells in a full-factorial design of four treatments (CTRL, QMR, a patient blood-derived secretome, and QMR+SECRETOME) two oxidative-stress states (basal and tert-butyl hydroperoxide [tBHP]-induced), and three time points (8, 24, 72 h). lncRNAs and circRNAs were sub-classified and mapped via GO enrichment and in silico ceRNA prediction. PCA identified QMR as the dominant driver of transcriptomic variance, priming ARPE-19 cells to integrate paracrine signals. Analysis across six factorial contrasts identified 105 modulated non-coding transcripts, including a pan-responsive antisense core (BASP1-AS1, SOD2-OT1) and condition-specific shifts in master lincRNAs (NEAT1, MALAT1). QMR+SECRETOME produced a distinct combinatorial transcriptomic signature. circASPH was exclusively upregulated by QMR, while circCRIM1 was preferentially hyperactivated by combinatorial treatment. ceRNA analysis predicted potential sponging of miR-29, miR-21, and miR-155, which may derepress BMP signaling and extracellular matrix remodeling. QMR reshapes the ARPE-19 non-coding transcriptome and enables a non-additive transcriptomic response to secretome co-treatment. The QMR-secretome-circRNA axis identifies candidate non-coding biomarkers and therapeutic targets for retinal regeneration.