Unique Ultrastructure Of Lacrimal Glands Of Nod And Balb/c Mice

Abstract

Abstract: : Purpose: The NOD mouse strain is increasingly being used as a model of Sjögrens Syndrome. Males are more affected than females and develop symptoms by 4 months of age. Unfortunately there has been essentially no literature addressing the morphological features of the lacrimal glands in these mice. The present study addresses this deficiency at the ultrastructural level. Methods: Lacrimal glands were collected from 1 and 4 month old, male NOD and control BALB/c mice and processed for light– and electron microscopy. Results: The histoarchitecture of the lacrimal gland in both strains of mice is unique in the organization of the lacrimal acini. Acinar lumena are exceedingly small and highly pleomorphic, i.e., evaginations from the central lumen extend nearly to the basement membrane enclosing the acini. In NOD mice, accumulations of lipid are present in the basal cytoplasm of lacrimal acinar cells at 1 month and are dramatically increased at 4 months. In 4 month NOD mice, large areas of cytoplasm are filled with pleomorphic, heterogeneous vacuoles containing membrane whorls and lipid fragments. Lipid inclusions within the basal cytoplasm of lacrimal acinar cells in BALB/c mice are either absent or minimal when compared to NOD mice and heterogeneous vacuoles are not present. Lymphocytic infiltration and destruction of acini is extensive in individual lobules of 4 month old NOD mice, although some lobule sparing occurs. Atypically shaped mitochondria and mitochondrial deterioration are evident in NOD mice. Conclusions: Although it has been established that symptoms mimicking Sjögrens Syndrome are evident in NOD mice by 4 months of age, our studies demonstrate alterations from normal cytology even in 1 month old NOD mice. Accumulations of lipid, vacuolization and mitochondrial deterioration in lacrimal acinar cells suggest cellular dysfunction occurring even at 1 month of age. CR: None. Support: NIH grants EY 10550 (JES), EY 11386 (SHA), DK48522 (Confocal Microscopy core, USC Center for Liver Disease), and a grant from the Sjögrens Syndrome Foundation (CD).

Keywords: lacrimal gland • microscopy: electron microscopy • inflammation