Proteomic profiling of human corneal stroma reveals molecular signatures associated with myopia progression

Myopia progression entails complex molecular changes in the ocular tissues, yet the stage-specific proteomic alterations in the human corneal stroma across different myopia stages remain largely uncharacterized. This study aimed to investigate proteomic profiles in corneal stroma samples obtained from patients undergoing small incision lenticule extraction (SMILE), including 19 low-myopia, 19 moderate-myopia, and 20 high-myopia cases. Using four-dimensional data-independent acquisition mass spec-trometry (4D-DIA-MS), we identified 3493 proteins, with 3248 common to all groups. Pairwise comparisons revealed 600, 767, and 309 differentially expressed proteins in the Moderate vs Low, High vs Low, and High vs Moderate groups, respectively. Functional enrichment indicated upregulated immune ac-tivation and protein synthesis pathways alongside downregulated metabolic and cyto-skeletal processes during myopia progression. A 14-protein signature derived from multinomial regression demonstrated strong capability to discriminate among the three severity groups in both training and test datasets. These findings reveal distinct, stage-specific proteomic remodeling in the corneal stroma during myopia progression, uncovering a prominent molecular shift toward enhanced protein synthesis and attenuated metabolic and structural regulation. The identified protein panel serves as a promising biomarker set for stratifying myopia severity and also represents potential novel therapeutic targets for myopia control.