Abstract

Recent evidence indicates that inflammatory cytokines and proteolytic enzymes play a vital role in the development of biomechanical failure in the cornea. Previous studies have shown that inflammatory cascades could be inhibited by peroxisome proliferator-activated receptor-α activation. This study seeks to investigate the biomechanical and structural features of the cornea in PPAR-α−/− mice and to assess alterations in inflammatory cytokines and enzymes. Adult PPAR-α −/− mice and wild-type C57BL/6 mice (WT) were used in this study. The corneas were excised and evaluated by modulus of elasticity test, enzymatic tissue digestion assay, corneal fluorescein sodium staining, tear film break-up time (tBUT), anterior segment OCT, in vivo corneal confocal microscopy (IVCM), transmission electron microscopy (TEM), and quantitative real-time PCR (RT-PCR). Decreased tBUT and SIt values were observed, while no corneal lesions were observed in the PPAR-α −/− mice. The corneal tangent modulus at fracture and resistance to enzymatic hydrolysis in PPAR-α −/− mice were significantly decreased ( P  = 0.005 and P  < 0.001, respectively). Anterior segment OCT showed that the corneas of PPAR-α −/− mice were significantly thinner than in the WT ( P  = 0.008). IVCM showed that the corneal nerve fibers of PPAR-α −/− mice were slender, and the hypo-reflective folds of the stromal layer were more apparent, while the stromal fibers of the WT were thicker. TEM showed that the lamellar stromal fibers were interlaced and disorganized with decreased fiber density in PPAR-α −/− mice compared with the WT. The expression of F-actin, lumican, laminin, TGF-β, TIMP-1, and TIMP-3 in the cornea of PPAR-α −/− mice was also decreased, accompanied by an increase of TNF-α and MMP-9. In conclusion, the corneal biomechanical stability and microstructural integrity of PPAR-α −/− mice were decreased, which might be associated with dysregulation of corneal structure-related components, inflammation-rel