Ocular surface disease and dacryoadenitis in aging C57BL/6 mice

Area of Science:

• Ophthalmology
• Immunology
• Gerontology

Background:

• Dry eye disease (DED) prevalence increases with age and in women.
• Aging is associated with various immune system dysfunctions.
• Understanding age-related DED mechanisms is crucial for developing targeted therapies.

Purpose of the Study:

• To investigate the development of DED in aged mice of both sexes.
• To identify age-dependent changes in ocular surfaces and lacrimal glands associated with DED.
• To determine the role of T cells in age-related DED pathogenesis.

Main Methods:

• Evaluation of ocular surface and lacrimal gland tissues from young, middle-aged, and elderly mice.
• Assessment of DED severity markers including corneal irregularity and barrier function.
• Analysis of immune cell infiltration (CD4(+), CD8(+), B cells) and gene expression (interferon-γ, IL-17).
• Adoptive transfer of CD4(+) T cells from elderly to young immunodeficient mice.

Main Results:

• An age-dependent DED phenotype was observed as early as 6-9 months in mice.
• Increased corneal irregularity, barrier disruption, conjunctival T-cell infiltration, and goblet cell loss were noted.
• Elderly male mice showed a type 1 T helper cell bias, while females exhibited a type 17 T helper cell bias.
• Lacrimal glands showed increased T cells and B cells, and decreased dendritic cells.
• Adoptive transfer of CD4(+) T cells from elderly mice induced DED in recipients, more so from male donors.

Conclusions:

• Aging mice develop a DED phenotype characterized by ocular surface changes and immune dysregulation.
• Pathogenic CD4(+) T cells accumulating with age play a critical role in transferring DED.
• Age-related autoimmunity is a significant contributor to the development of DED in aging populations.