Altered Tear Composition in Smokers and Patients With Graves Ophthalmopathy

Abstract

To analyze, compare, and contrast tear composition in healthy nonsmokers, smokers who were otherwise healthy, and patients with Graves disease (GD) accompanied by Graves ophthalmopathy (GO) of varying severity. Methods: Reflex tears were collected using Schirmer strips from 37 healthy nonsmokers, 33 otherwise healthy smokers, 51 patients with GD, and 85 patients with GO. Thyrotropin receptor-stimulating activity and serum thyroidstimulating antibodies were measured. Pooled tear samples from healthy nonsmokers, healthy smokers, and patients with GO were separated by means of electrophoresis. Proteins expressed in healthy smokers, patients with GO, and healthy nonsmokers were separated by means of electrophoresis and analyzed by mass spectrometry. Results: Based on the 97th percentile of findings from healthy nonsmokers, specific thyrotropin receptorstimulating activity was detected in 25% of the tear samples from healthy smokers, 32% of those from patients with GD, and 41% of those from patients with GO. Clinical activity scores correlated with serum thyroidstimulating antibody levels but not tear thyrotropin receptor-stimulating activity. Electrophoresis revealed additional proteins of 30 to 41 kDa in the tear samples from patients with GO and healthy smokers compared with samples from healthy nonsmokers. These proteins were identified as zinc-␣2-glycoprotein and lactoferrin but have no thyrotropin receptor-stimulating activity. Conclusions: We demonstrate similar changes in tear composition in patients with GO and healthy smokers compared with healthy nonsmokers. Expression of zinc-␣2glycoprotein and lactoferrin is increased and their molecular weights are modified, suggesting degradation and/or changes during glycosylation, which may affect the bioactivities of zinc-␣2-glycoprotein and lactoferrin. Clinical Relevance: Smoking, which is a significant risk factor for the development of GO, modifies tear composition.

Tear proteomics in evaporative dry eye disease

“…30 The exact function of ZAG in tears and its possible role in lipid degradation have only been postulated and not completely clarified. 31,32 In our study, we detected ZAG in both patients and controls, with no statistically significant differences in the respective expression. Our data, do not suggest any significant role of ZAG in the tear stability mechanism, at least as far as mild dry eye is concerned.…”

Analysis of protein composition and protein expression in the tear fluid of patients with congenital aniridia

“…The altered abundance of this protein in tears was found in several pathological eye conditions. For example, increased abundance of ZAG was found in the tears of keratoconus patients [15], in patients with Grave's ophthalmopathy [41] or keratitis [42]. On the other hand, no significant changes of this protein were noticed in tears from patients with dry eye syndrome [43].…”

Inflammatory cytokine profiles in the tears of thyroid-associated ophthalmopathy

“…Many studies have found evidence that the lacrimal gland and tear fluid may be directly involved in the ocular surface damage in TAO [6][7][8][9][10][11][12][13][14]. Eckstein [6] found that ocular surface damage in TAO correlates with reduced tear production, and acinar cells from lacrimal glands were positive for thyotropin receptor (TSH-R), which is considered a target of autoimmunity shared by both thyroid and extrathyroidal sites in TAO.…”