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DR), apoptosis markers (i.e. Fas), and the infl ammatory cytokine IL-6 by
the conjunctival epithelial cells (Brignole et al. 2001, Turner et al. 2000). The
numbers of CD3, CD4, and CD8-positive T lymphocytes in the conjunctiva
decreased in cyclosporine-treated eyes, while vehicle-treated eyes showed
an increased number of cells expressing these markers (Kunert 2002).
Following treatment with 0.05% cyclosporine, there was a signifi cant
decrease in the number of cells expressing the lymphocyte activation
markers CD11a and HLA-DR, indicating less activation of lymphocytes
compared with vehicle-treated eyes.
In December 2002, US Food and Drug Administration approved CsA
0.05% ophthalmic emulsion for treatment of dry eye disease and it has been
a record number of prescriptions in the USA and worldwide.
Essential Fatty Acids
Essential fatty acids are necessary for complete health and they cannot be
synthesized by vertebrates and must be obtained from dietary sources.
Among the essential fatty acids are 18 carbon omega-6 and omega-3 fatty
acids. In the typical western diet, 20-25 times more omega-6 than omega-3
fatty acids are consumed. Omega-6 fatty acids are precursors for arachidonic
acid and certain pro-infl ammatory lipid mediators (PGE 2 and LTB4). In
contrast, certain omega-3 fatty acids (e.g. EPA found in fi sh oil) inhibit
the synthesis of these lipid mediators as well as block production of IL-1
and TNF-α (Endres et al. 1989, James 2000). A benefi cial clinical effect of
fi sh oil omega-3 fatty acids on rheumatoid arthritis has been observed in
several double-masked placebo-controlled clinical trials (James and Cleland
1997, Kremer 2000). In a prospective placebo-controlled clinical trial of the
essential fatty acids linoleic acid and gamma-linoleic acid administered
orally twice daily produced signifi cant improvement in ocular irritation
symptoms (Macsai 2008) and ocular surface lissamine green staining
(Barabino et al. 2003).
Anti-infl ammatory Therapy in Mice: Lessons from Animal
The use of mice in dry eye research has increased steadily over the last
twenty years. Despite size disparity, the similarities in the anatomic structure
of human and mouse eye greatly outweigh the differences. Also, the
immunological system of both human and mice share more similarities than
disparities, which make mice an ideal candidate to study immunological
responses. A good accumulation of data of infl ammation and dry eye disease
came from animal models of SS. Several candidate compounds for dry eye
treatment have been fi rst evaluated in mice for effi cacy in treating corneal
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