Abstract
Purpose: :
Healthy conjunctiva secreting mucins is essential for maintaining the integrity of the ocular surface epithelium. We used the Sod1(-/-) mice deficient in Cu, Zn - superoxide dismutase 1 (SOD1) and investigated the effect of oxidative stress on the conjunctival phenotype/ocular surface health and tear functions.
Methods: :
Fifty weeks old C57/B6 wild type mice (wt) and Sod1(-/-) mice were used for evaluations of the tear film break-up time (BUT), fluorescein staining of the cornea, and the periodic acid Schiff (PAS) staining of the conjunctival specimens to detect goblet cell densities in the conjunctiva. Immunohistochemistry staining with anti-MUC5AC and anti-4-hydroxy-2-nonenal (4HNE) antibodies were also performed.
Results: :
The mean BUT value was 2.8±1.5s and 3.8±0.8s in the Sod1(-/-) and wt mice, respectively (p< 0.05). The respective corneal fluorescein staining score was 5.0±1.6 and 3.3±1.0 points, respectively (p< 0.05). The conjunctiva of Sod1(-/-) mice showed marked thickening of conjunctival epithelium and keratinization. The goblet cell density in the wt mice was 58.9±24.7 compared to 4.8±5.1 cells/ fornix in the Sod1(-/-) mice, respectively (p< 0.05). The number of cells positively stained with MUC5AC were significantly lower in the Sod1(-/-) mice (2.6±2.7 cells/fornix) compared to the wt mice (12.3±4.9 cells/fornix) (p < 0.05). Conjunctival epithelium in Sod1(-/-) mice displayed marked staining with 4HNE antibodies.
Conclusions: :
Marked tear instability with decreased MUC5AC secreting goblet cells, corneal epithelial damage and increased lipid oxidation were the prominent features of the ocular surface disease in the Sod1(-/-) mice. Elevated conjunctival oxidative stress status appears to affect the conjunctival mucin secretions and the epithelial phenotype. Sod1(-/-) mice may serve as a good model for mucin deficient dry eye disease.
Keywords: cornea: tears/tear film/dry eye • oxidation/oxidative or free radical damage • conjunctiva