The role of oxidative stress and inflammation in the pathogenesis of dry eye

Dry eye is a multifactorial disease of the tears and the ocular surface that results in symptoms of discomfort,visual disturbance, and tear film instability with potential damage to the ocular surface. Increased osmolarityof the tear film and inflammation in the lacrimal system and ocular surface are important operational factors inthe genesis of some dry eye disorders. Mechanical abrasion secondary to tear deficiency may create aninflammatory environment where conjunctival epithelial cells and lymphocytes are stimulated to produce andsecrete various cytokines into the tear film. Elevated cytokine levels within the tear film, combined with reducedconcentrations of essential lacrimal-gland derived factors such as epidermal growth factor (EGF) andretinol create an environment in which terminal differentiation of the ocular surface epithelium is impaired.The histopathologic changes in the minor salivary gland and lacrimal gland biopsy are characterized by focaland/or diffuse lymphoid cell infiltrates and parenchymal destruction. The majority of cells in glandular biopsyspecimens are CD4+ cells with a small proportion of CD8+T-cells.<BR>Apoptosis of acinar cells and inflammatory cells are also key events in relation to development of dry eyes.We previously showed the presence of apoptosis of acinar cells, FasL expression in lacrimal glands and thatthe FasL expression highly correlated with glandular function especially in those patients without glandularenlargement. FasL expression of infiltrating lymphocytes were low in the lacrimal glands of patients with SSwith enlarged exocrine glands where the lacrimal gland function was well preserved even with massive lymphocyteinvasion. In other words, the infiltration of lymphocytes alone did not cause glandular dysfunction.Apoptosis of acinar cells may explain these differences. Oxidative stress is recently receiving the attention ofresearchers and clinicians as a possible mechanism in the development of dry eye disease. Tsubota et alhave shown, for the first time in the literature, increases in oxidative stress markers, changes in antioxidantrelatedgene expression, and discordance in differentiation capacity in corneal epithelia in dry eye conditions,suggesting a strong relationship between the accumulation of oxidative stress and the etiology of cornealepithelial alterations in blink-suppressed dry eye. The management of oxidative stress may provide a newapproach for the prevention and therapeutic treatment for dry eye syndromes. The increased awareness ofoxidative stress related to disease and the need to measure the delicate balance that exists between freeradicals and the systems in place to regulate them has given rise to a demand for new research tools.