Abstract
Purpose :
Older age is a significant risk factor for developing dry eye disease (DED). The mouse is a commonly used animal model to study DED. In this study, age-related histopathology in human lacrimal glands (LGs) was investigated and the difference between human and mouse LG aging was compared.
Methods :
Human LGs were retrieved from cadaver donors, six males (ages 66 to 80) and one female (age 89). The 24 to 29 month-old C57BL/6J male mice (n=6), corresponding to 70 to 80 year-old humans, were used in the study. The age-associated pathologic changes in LGs were examined by histology. Specific cell types in LGs were determined by immunostaining against biomarker proteins.
Results :
Acinar atrophy was seen in all aged human LGs with severity ranging from moderate to severe among the individuals. Lysozyme, a major tear fluid protein, was evenly distributed in the cytoplasm of acinar cells of the moderately atrophic LGs but aggregated in the basal lateral side of the acinar cells of the severely atrophic LGs. In the LGs of aged male mice, lysozyme expression was significantly decreased or absent in some of the acinar lobules. These results suggest that acinar atrophy or dysfunction is likely related to the decrease of protein levels in the tear fluids during LG aging. In aged human LGs, the alpha smooth muscle actin (αSMA)-positive myoepithelial cells were present bordering the basal lamina of the acinar epithelial layer. In contrast, the aSMA-positive myoepithelial cells were absent in some areas of the aged mouse LGs. The additional differences between the aged human and mouse LGs include: 1) periductal and periacinar fibrosis were prominent in the aged human LGs, but not the mouse LGs. 2) fatty cell infiltration was seen in all the human LGs, but not the mouse LG samples. In the severe case, over 50% of the acinar area was replaced by the fatty tissue. 3) Focal lymphocyte infiltration was only identified in one of the seven human LG samples but was largely present in all the mouse LG samples.
Conclusions :
Acinar tissue atrophy and periductal fibrosis are the significant pathologic changes in aged human LGs. Fatty cell infiltration and replacement of acinar tissues were common in human, but not mouse LGs. Our study suggests that lacrimal gland aging in humans and mice shared both common and different underlying pathogenic mechanisms. More human LG samples from both sexes are being collected for the study.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.