The effect of cigarette smoke constituents on the expression of HLA-DR in orbital fibroblasts derived from patients with Graves ophthalmopathy.

PURPOSE: Numerous studies have established a strong association between smoking and Graves disease, but the underlying mechanism of Graves ophthalmopathy has not been elucidated. Recent studies of Graves ophthalmopathy have focused on the orbital fibroblast as an integral component in the pathogenesis of this disorder. This investigation focuses on the effect of cigarette smoke constituents, nicotine and tar, to alter the expression of human leukocyte antigen (HLA-DR) in cultured orbital fibroblasts from patients with Graves disease. METHODS: HLA-DR expression was quantified by scanning densitometry of whole cell lysates subjected to sodium dodecyl sulfate--polyacrylamide gel electrophoresis with immunoblotting and also by direct immunofluorescence. RESULTS: Cultured orbital fibroblasts, obtained from patients undergoing orbital decompression for severe Graves ophthalmopathy, failed to express HLA-DR as analyzed by both immunoblotting and direct immunofluorescence when treated with nicotine alone (25-300 ng/ml). The expression of HLA-DR increased three-fold when nicotine (25 ng/ml) in combination with interferon-gamma (500 U/ml) was added to the cultured orbital fibroblasts (p < 0.0001). Cultured orbital fibroblasts treated with tar alone (60-600 ng/ml) failed to exhibit HLA-DR expression as assessed by direct immunofluorescence and immunoblotting. A greater than two-fold increase in HLA-DR expression occurred when tar (600 ng/ml) combined with interferon-gamma (500 U/ml) was added to the cultured orbital fibroblasts (p < 0.0001). CONCLUSION: The results suggest a possible molecular mechanism for the more severe ophthalmopathy observed in Graves patients who smoke cigarettes. These findings could prove useful for possible medical interventions to decrease or even inhibit the interaction between cigarette constituents, cytokines, and orbital fibroblasts.

Levator aponeurosis elastic fiber network.

This light and electron microscopic study demonstrates an elastic fiber network (EFN) for the levator palpebrae superioris muscle complex, which forms an intricate insertion into the upper eyelid. The EFN is examined in the monkey, in a fresh exenteration specimen, and in fresh frozen cadaver specimens from both sexes of different age groups. Multiple elastic insertions of the levator aponeurosis and Muller's muscle attachment with well-organized elastic fibers are demonstrated using special staining techniques and serial microscopic sectioning. Transmission electron microscopy (TEM) confirms the ultrastructure of "mature" elastin fibers in Muller's muscle tendon and their close relationship with the elastin-related fiber, oxytalan. Current thinking concerning the nature of elastic fibers and their possible implications in acquired involutional blepharoptosis is discussed. This microscopic study of the EFN of the upper eyelid focuses attention on the multiple elastic fiber insertions of the levator muscle complex that includes the levator aponeurosis, the conjoined fascia, the lid crease area, and Muller's muscle tendon, which have not been previously described.

Congenital lacrimal fistula.

Congenital lacrimal fistula is a rare developmental condition. Patients may be asymptomatic or have tearing from the fistula, the eye or both. The clinical features of 60 patients are reviewed, including presenting symptoms, presence of other lacrimal or systemic anomalies and morphology of the fistula. A detailed description is given of the surgical technique utilised in patients whose symptoms warrant surgical intervention. The results of this technique are presented and alternative treatment strategies are discussed. Theories of the aetiology of the condition are reviewed and morphological and histological evidence is presented to support our belief that congenital lacrimal fistulae represent aberrant canaliculi.