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      Interleukin-6 levels in the conjunctival epithelium of patients with dry eye disease treated with cyclosporine ophthalmic emulsion.

      Cornea
      Administration, Topical, Biological Markers, Conjunctiva, metabolism, pathology, Cyclosporine, therapeutic use, DNA Primers, chemistry, Double-Blind Method, Dry Eye Syndromes, drug therapy, Emulsions, Epithelium, Glyceraldehyde-3-Phosphate Dehydrogenases, Humans, Immunosuppressive Agents, Interleukin-6, genetics, Prospective Studies, RNA, Messenger, Reverse Transcriptase Polymerase Chain Reaction

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          Abstract

          To evaluate interleukin-6 (IL-6) levels in the conjunctival epithelium of patients with moderate to severe dry eye disease before and after treatment with cyclosporin A ophthalmic emulsion (CsA) or its vehicle. Conjunctival cytology specimens were obtained from a subset of patients enrolled in a 6-month randomized, double-masked clinical trial of the efficacy and safety of topical CsA at baseline and after 3 and 6 months of B.I.D. treatment with 0.05% cyclosporine emulsion (n = 13), 0.1% cyclosporine emulsion (n = 8), or vehicle (n = 10). RNA was extracted and a competitive reverse transcriptase polymerase chain reaction (RT-PCR) was used to evaluate the levels of mRNA encoding the inflammatory cytokine IL-6 and a housekeeping gene, G3PDH. Levels of IL-6 and G3PDH were measured and compared. There was no change from baseline in the level of G3PDH after 3 or 6 months in any group. IL-6 normalized for G3PDH (IL-6/G3PDH ratio) was not different from baseline at 3 months but showed a significant decrease from baseline in the group treated with 0.05% CsA (p = 0.048) at 6 months. No significant between-group differences were noted and no correlation was observed between the change in IL-6/G3PDH and corneal fluorescein staining. This preliminary, small-cohort study showed a decrease in IL-6 in the conjunctival epithelium of moderate to severe dry eye patients treated with 0.05% CsA for 6 months. The observed decrease suggests that dry eye disease involves immune-mediated inflammatory processes that may be decreased by treatment with topical ophthalmic cyclosporine.

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          The Pathology of Dry Eye

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            Altered cytokine balance in the tear fluid and conjunctiva of patients with Sjögren's syndrome keratoconjunctivitis sicca

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              Senile atrophy of the human lacrimal gland: the contribution of chronic inflammatory disease.

              Histological examination of 99 human lacrimal glands showed a relationship between atrophy of the secretory acini and secretory duct obstruction, ascending periductal fibrosis, and obliteration of the adjacent blood vessels caused by lymphocytic and polymorphonuclear inflammation. Investigation of the subgroups of the B lymphocytic series by immunohistochemistry did not show any statistical change with age, sex, fibrosis, or lymphocytic inflammation. The concept of senile atrophy occurring as a result of senescent involution of the lacrimal gland is challenged on the basis of the histological findings.
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