Age-related Autoimmune Changes in Lacrimal Glands

Abstract

Aging is a complex process associated with dysregulation of the immune system and low levels of inflammation, often associated with the onset of many pathologies. The lacrimal gland (LG) plays a vital role in the maintenance of ocular physiology and changes related to aging directly affect eye diseases. The dysregulation of the immune system in aging leads to quantitative and qualitative changes in antibodies and cytokines. While there is a gradual decline of the immune system, there is an increase in autoimmunity, with a reciprocal pathway between low levels of inflammation and aging mechanisms. Elderly C57BL/6J mice spontaneously show LGs infiltration that is characterized by Th1 but not Th17 cells. The aging of the LG is related to functional alterations, reduced innervation and decreased secretory activities. Lymphocytic infiltration, destruction, and atrophy of glandular parenchyma, ductal dilatation, and secretion of inflammatory mediators modify the volume and composition of tears. Oxidative stress, the capacity to metabolize and eliminate toxic substances decreased in aging, is also associated with the reduction of LG functionality and the pathogenesis of autoimmune diseases. Although further studies are required for a better understanding of autoimmunity and aging of the LG, we described anatomic and immunology aspects that have been described so far.

Comparative Analysis of Age-Related Changes in Lacrimal Glands and Meibomian Glands of a C57BL/6 Male Mouse Model

“…The changes in effector T cells were accompanied by increased populations of activated antigen-presenting cells in the DLNs, suggesting that an increased presence of the antigen is crucial to age-related dry eye, as previously reported [4]. High levels of IFN-γ in the conjunctiva are known to impact the loss of goblet cells [5,12]. Our study showed a decreased goblet cell density in 1Y-old mice, along with an increase in CD4 + IFNγ + cells in LG.…”

“…Chronological changes in the LGs were reported in mice with mast cell infiltration, decreased peroxidase secretion, and lipofuscin accumulation at 8 to 12 months of age, followed by T and B lymphocytic infiltration, decreased innervation, decreased acetylcholine release, and structural changes up to 24 months of age [5,11,12]. Given the post-mortem changes in the LGs in humans, C57BL/6 mice can be used as a model to evaluate age-related DED, since C57BL/6 mice develop age-related dacryoadenitis, MG dysfunction, and corneal staining [5]. Interestingly, an aging-related predominance of IFN-γ-secreting CD4 + IFNγ + or CD4 + IL17 + cells in the LGs may depend on the sex of the rodent [5,12].…”

“…Aging impairs the LGs by altering multiple mechanisms, such as neuroendocrine, immunological, apoptotic, protein secretion, and oxidative stress pathways [11]. Chronological changes in the LGs were reported in mice with mast cell infiltration, decreased peroxidase secretion, and lipofuscin accumulation at 8 to 12 months of age, followed by T and B lymphocytic infiltration, decreased innervation, decreased acetylcholine release, and structural changes up to 24 months of age [5,11,12]. Given the post-mortem changes in the LGs in humans, C57BL/6 mice can be used as a model to evaluate age-related DED, since C57BL/6 mice develop age-related dacryoadenitis, MG dysfunction, and corneal staining [5].…”

“…Given the post-mortem changes in the LGs in humans, C57BL/6 mice can be used as a model to evaluate age-related DED, since C57BL/6 mice develop age-related dacryoadenitis, MG dysfunction, and corneal staining [5]. Interestingly, an aging-related predominance of IFN-γ-secreting CD4 + IFNγ + or CD4 + IL17 + cells in the LGs may depend on the sex of the rodent [5,12]. This study corroborated the previous findings on age-related inflammatory changes in the LGs with a predominance of CD4 + IFNγ + cells in male mice.…”

“…The aging-dependent changes in the ocular surface with DED are related to biological changes in the lacrimal glands (LGs) and meibomian glands (MGs). Although the pathogenesis of aging-associated DED has not yet been fully understood, recent studies have shown that autoimmune changes or oxidative stress in the LGs and acinar cell atrophies in the MGs occur with aging [4][5][6][7][8].…”