To Dry Eye Disease Sjogrens Syndrome

The lacrimal gland is an associated gland of the ocular surface that functionally and embryolog-ically constitutes an integral part of the ocular surface. Similarly, from the viewpoint of mucosal immunology, it is an integral part of the ocular mucosal immune system (EALT) [23] together with the conjunctiva-associated lymphoid tissue (CALT) and the lacrimal drainage-associated lymphoid tissue (LDALT). It contains similar cell populations of T- and B-lymphocytes and DC [64].

T-cell-mediated inflammatory alterations of the lacrimal gland have been known for a long time; they appear to be associated with an impairment of the innervation that triggers the final release of aqueous secretion, and Sjogren's syndrome is a major cause for tear deficiency [7]. Alterations of B-lymphocytes are also described in Sjogren's syndrome. The aetiology of the disease is unknown, but it may originate from activation of the acinar epithelial cells due to viral infection by Epstein-Barr [52] or other viruses which stimulate a production of inflammatory cytokines and can lead to presentation of epithelial autoantigens by upregulated MHC-class-II and ICAM-1 production and expression at the epithelial surface. A number of respective autoantigens are characteristic for Sjogren's syndrome and can be used to support the diagnosis (e.g. SS-A, SS-B, a- and b-fodrin, M3 receptor). A distinct repertoire of antigen receptors was found on T and B cells in Sjogren's patients. This can lead to a breakdown of the physiological peripheral self-tolerance and results in an activation of lymphocytes that carry receptors for self antigens and happen to have escaped the central tolerance mechanisms in primary lymphoid tissues. An accumulation of mainly CD4+ T-helper cells, DC and smaller amounts of B cells in the salivary and lacrimal glands has been reported [46]. This results in the destruction of acinar epithelial tissue by binding of the self-intolerant cytotoxic T cells to acinar cells and lymphocyte induction of acinar apoptosis via release of cytotoxic molecules. The lymphocytes, and to a certain extent also epithelial cells, produce a large amount of mainly inflammatory Thi-type cytokines (IL-2, IL-6, IFN-g, TNF-a). Th2 cytokines (IL-4, IL-5, IL-10) are produced in smaller amounts and preferably in areas of occasional B-cell accumulations [43]. The presence of inflammatory cytokines induces a further influx of more lymphocytic cells by upregulation of adhesion molecules on glandular vessels and leads to an activation of stromal cells with release of matrix metallopro-teinases that cause a degenerative remodelling of the extracellular matrix around the epithelial acini.

Since only about half of the secretory acinar cells are destroyed by this process, it appears likely that the remaining intact acinar cells are inhibited from secretion by negative interference with innervation [7, 8]. Suggested mechanisms include an observed reduction of density of innervating nerve fibres, the inhibition of release of neurotransmitters by inflammatory cytokines or the blockade of innervation effects in the epithelial cells by autoantibodies against their muscarinic M3 receptor [7].

Androgen deficiency is shown as an important predisposing factor for the initiation of inflammatory reactions as well as alterations of the secretion of the lacrimal and meibomian glands resulting in tear deficiency [60].

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