May 2004
Volume 45, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2004
Lacrimal acini in NOD mice exhibit profound alterations in mature secretory vesicles
Author Affiliations & Notes
  • S.R. da Costa
    Pharmaceutical Sciences,
    University of Southern California, Los Angeles, CA
  • M. Pidgeon
    Cell and Neurobiology,
    University of Southern California, Los Angeles, CA
  • M. Mac Veigh
    Medicine/GI and Liver,
    University of Southern California, Los Angeles, CA
  • C. Ding
    Cell and Neurobiology,
    University of Southern California, Los Angeles, CA
  • J. Schechter
    Cell and Neurobiology,
    University of Southern California, Los Angeles, CA
  • S. Hamm–Alvarez
    Pharmaceutical Sciences,
    University of Southern California, Los Angeles, CA
  • Footnotes
    Commercial Relationships  S.R. da Costa, None; M. Pidgeon, None; M. Mac Veigh, None; C. Ding, None; J. Schechter, None; S. Hamm–Alvarez, None.
  • Footnotes
    Support  NIH grants EY–11386, EY–10550, P30 DK48522 and PD/6281/2001
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 3857. doi:
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      S.R. da Costa, M. Pidgeon, M. Mac Veigh, C. Ding, J. Schechter, S. Hamm–Alvarez; Lacrimal acini in NOD mice exhibit profound alterations in mature secretory vesicles . Invest. Ophthalmol. Vis. Sci. 2004;45(13):3857.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: NOD mice are established models for investigation of the pathogenesis of Sjögrens syndrome. In this model, males are more affected than females and develop symptoms of impaired functioning and lymphocytic infiltration of the lacrimal and salivary glands by 4 months of age. To better understand the cellular events that initiate lacrimal gland dysfunction, we investigated the abundance and morphology of mature secretory vesicles (SVs) in age–matched male BALB/c and NOD mice. Methods: Cryosections from lacrimal glands from 1 and 4 month male BALB/c and NOD mice were processed for confocal fluorescence and electron microscopy (EM) evaluation of SV abundance and morphology. Lacrimal gland lysates were processed by SDS–PAGE and Western blotting for evaluation of changes in the SV marker, rab3D. Results: Rab3D immunofluorescence associated with 1–2 µm SVs was distributed abundantly throughout the cytoplasm with an enrichment beneath apical membranes in lacrimal acini from 1 and 4 month BALB/c mice, with minor increases and decreases, respectively, in SV heterogeneity and the intensity of labeling in the older mice. In contrast, Rab3D immunofluorescence in lacrimal acini from 1 and 4 month NOD mice was associated with a more heterogeneous population of SVs exhibiting apparent irregularities in the continuity of labeling relative to BALB/c mice; the intensity of rab3D labeling in NOD mice relative to age–matched BALB/c mice was also markedly decreased. EM analysis confirmed the profound changes in SV morphology in NOD mice, revealing many irregularly shaped and unusually large SVs formed. Quantitation of multiple SVs (246–338 from 10–17 randomly acquired EM images under each experimental condition) into single vesicles, double vesicles and multiple vesicular aggregates revealed a striking increase in the percentage of SVs that had undergone apparent premature cytoplasmic fusion into multiple vesicular aggregates from 11 and 13% of total vesicles, respectively, in 1 and 4 m BALB/c mice to 42 and 77% of total vesicles, respectively, in 1 and 4 m NOD mice. These changes were not associated with altered rab3D expression. Conclusion: NOD mice exhibit decreased intensity of labeling of SVs with the secretory effector, rab3D, in parallel with an apparent premature cytoplasmic fusion of SVs of altered morphology.

Keywords: lacrimal gland • cytoskeleton • cell membrane/membrane specializations 
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