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symptoms, blurred and fl uctuating vision, tear fi lm instability, increased
tear osmolarity and ocular surface epithelial disease (de Paiva 2003, Goto
et al. 2002, Musch 1983, Pfl ugfelder et al. 1998). It is often a challenging
clinical problem to identify because of its varying clinical presentation. Dry
eye impacts quality of life by decreasing functional vision, i.e. the ability
to perform daily activities such as reading, using a computer and driving
(Miljanovic et al. 2007).
There is an increasing evidence that dry eye is an infl ammatory disease.
Disease or dysfunction of the tear secretory glands leads to changes in tear
composition, such as hyperosmolarity that stimulate the production of
infl ammatory mediators on the ocular surface (Luo et al. 2004). Infl ammation
may in turn cause dysfunction or disappearance of cells responsible for
tear secretion or retention (Niederkorn et al. 2006). Infl ammation can also
be initiated by chronic irritative stress (e.g. contact lenses) and systemic
infl ammatory/autoimmune disease (e.g. rheumatoid arthritis). Regardless
of the initiating cause, a vicious cycle of infl ammation may develop on the
ocular surface in dry eye that leads to ocular surface disease.
Pathogenesis of Dry Eye: Role of Infl ammation
The dry eye fi eld is undergoing a transformation due to increased knowledge
of molecular and cellular mechanisms of dry eye. Increased infl ammatory
cytokines, tear film osmolarity, metalloproteinases, chemokines and
chemokines receptors infl ammatory cascade and activation of immune
cells have been implicated in the pathogenesis of dry eye.
Increased Infl ammatory Cytokines
Increased production and activation of pro-inflammatory cytokines
(interleukin [IL]-1 and tumor necrosis factor [TNF]-α) and proteolytic
enzymes by stressed ocular surface and glandular epithelial cells, as well
as by the infl ammatory cells that infi ltrate these tissues have been reported
in dry eye (Lopez and Ubels 1991, 1993, Zhu et al. 2004).
Increased concentration of pro-infl ammatory cytokines and chemokines
in the tear fl uid, such as IL-6, IL-1, and TNF-α has been extensively reported
(Baudouin et al. 2005, de Paiva et al. 2007, Jones et al. 1994, Niederkorn et al.
2006, Pfl ugfelder et al. 1999, Rolando et al. 2005, Solomon et al. 2001, Stern et
al. 2002, Yoon et al. 2007). In humans, signifi cantly increased levels of IL-1α,
IL-6, IL-8, TNF-α and transforming growth factor (TGF)-β1 RNA transcripts
have been found in the conjunctival epithelium of Sjögren's syndrome, the
most severe type of dry eye, compared to controls (Pfl ugfelder et al. 1999).
However, the exact role of these cytokines in dry eye has not been fully
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