Increased Nitric Oxide Synthase Expression and Nitrogen Related Oxidant Formation in Conjunctival Epithelium of Dry Eye (Sjögren's Syndrome)

Abstract

Purpose:: Dry eye is a chronic disease with a deficiency of tears which may lead to ocular surface dysfunction. The factors leading to the aqueous tear deficiency are complex involving autoimmune disease (i.e. Sjögren's syndrome, SS), loss of hormonal support, and glandular inflammation. Until now, the expression of nitric oxide synthases and possible role of nitric oxide in the human dry eye has not been investigated. Therefore, purpose of this study was to examine reactive nitrogen species in conjunctival epithelial cells of dry eye.

Methods:: The eyes of patients suffering from autoimmune dry eye (SS) participated in our study (moderate dry eye with reversible slit lamp signs and less or more evident symptoms of dryness). Normal eyes served as controls. Conjunctival epithelial cells were obtained by the method of impression cytology. In conjunctival epithelium nitric oxide synthase isomers (NOS), enzymes generated nitric oxide, nitrotyrosine, a cytotoxic byproduct of nitric oxide and malondialdehyde, a byproduct of lipid peroxidation, were examined immunohistochemically.

Results:: In contrast to normal eyes where endothelial nitric oxide synthase (NOS3) as well as inducible nitric oxide synthase (NOS2) are only slightly expressed in the conjunctival epithelium, in dry eye NOS3 as well as NOS2 are gradually expressed along the severity of dry eye symptoms. Peroxynitrite formation (demonstrated by nitrotyrosine residues) and lipid peroxidation (evaluated by increased malondialdehyde staining) are also found in dry eye with pronounced symptoms of dryness.

Conclusions:: Results point to the suggestion that reactive nitrogen species are involved in the pathogenesis or self-propagation of autoimmune dry eye (SS).

Clinical Trial:: Ministry of Health of the Czech Republic

Keywords: immunohistochemistry • nitric oxide • conjunctiva