Objective      To investigate the relationship of gender differences with severity of dry eye phenotype and histopathological changes of ocular surface in the C57BL/6.NOD-Aec1Aec2 mice (a mouse model of Sjögren’s syndrome).       Methods      Totally 45 female and 45 male C57BL/6.NOD-Aec1Aec2mice were used in the study. Schirmer’s test Ⅰ

corneal fluorescein staining and scoring

Hematoxylin-eosin (HE) staining

counting for inflammatory cells in the lacrimal gland

and scanning electron microscopy for corneal epithelial cells and microvilli were performed in postborn 4

8

12

16 and 20 weeks.       Results      Both the female and male mice had no sign of dry eye at the age of 4 weeks. Since the 8th week

tear secretion became decreased which the stained grade of corneal fluorescein increased with the age growth in both gender groups. HE staining showed damaged structures of the ducts and acinar and severer infiltration of inflammatory cells in lacrimal glands. Scanning electron microscopy displayed dropped corneal epithelial cells

diminished microvilli and loosen or interrupted intercellular junctions. At the age of 16 weeks

the male mice had significantly decreased tear secretion (P=0.035)

increased stained grade of corneal fluorescein (P=0.028) and more inflammatory cells (P=0.017) when compared with the female mice at the same age.       Conclusion       The signs of dry eye are more severe in the female C57BL/6.NOD-Aec1Aec2 than male mice

which may be related to the changes of estrogen levels.