Molecular mechanisms of cold stress-induced lens opacity: An investigation through multi-omics integrative analysis.

Abstract

Cold exposure accelerates lens protein aggregation through epigenetic modulation and metabolic dysregulation. However, existing research has primarily focused on the mechanisms of protein phase separation; the molecular mechanisms underlying cold-induced reversible lens opacity remain inadequately characterized. This study aimed to elucidate the dynamic regulatory network of lens responses to cold exposure. Using a male Wistar rat model subjected to cold stress, we investigated molecular alterations through integrated transcriptomic and metabolomic analyses. Our findings demonstrate that cold stress induces reversible lens opacity. Multi-omics analysis revealed that hypothermia disrupts cellular signaling pathways, with particular emphasis on calcium signaling. Biomarker quantification showed decreased levels of phosphatidylcholine (PC), ginkgolide A, and glycine-proline-hydroxyproline, while D/L-cysteine, nicotinamide adenine dinucleotide (NADH), and L-cysteinylglycine disulfide were elevated. These results establish the molecular mechanisms of cold stress-induced reversible lens opacity, emphasizing the critical roles of calcium-ROS coupling and membrane lipid metabolism. This provides a novel mechanistic framework distinct from classical protein aggregation models.