Complement-mediated inflammation and mitochondrial energy metabolism in the proteomic profile of myopic human corneas

Myopia is one of the most common causes of visual impairment worldwide. To identify proteins related to myopiagenesis, data-independent acquisition proteomic analysis was performed using corneal lenticules of myopic patients who underwent small incision lenticule extraction surgery. A total of 19 lenticules from 19 age and sex-matched patients were analyzed, 10 in high refractive error (HR, spherical equivalent over -6.00 D) group and 9 in low refractive error (LR, spherical equivalent between -3.00 and - 1.00 D) group. Differentially expressed proteins (DEPs) were identified by comparing the corneal proteome between the two groups. Functional analyses were performed to explore the biological pathways and interactions of the DEPs. 107 DEPs (67 upregulated and 40 downregulated in HR group, compared to LR) were identified from 2138 quantified proteins. Functional analyses indicated that upregulated proteins were primarily involved in the complement pathways and extracellular matrix (ECM) remodeling, while downregulated proteins were involved in mitochondrial energy metabolism. Western blot analysis confirmed increased complement C3a and apolipoprotein E in HR samples, further supporting the proteomics data. In conclusion, this proteomic study reveals that proteins associated with the complement system, ECM remodeling, and mitochondrial energy metabolism might be key effectors in myopiagenesis. SIGNIFICANCE: Myopia has become one of the most prevalent causes of visual impairment, especially in Asia. The underlying mechanism of myopia development is still up for debate. This study compares the proteomic profiles of high and low myopic corneas, identifying differentially expressed proteins associated with the complement system, ECM remodeling, and mitochondrial energy metabolism. The findings of this study could provide novel insights into the pathogenesis of myopia. The complement system and mitochondrial energy metabolism may provide potential therapeutic targets in the treatment and prevention of myopia.