Expression of LIGHT/TNFSF14 and Its Receptors, HVEM and LTβR, Correlates with the Severity of Fibrosis in Lacrimal Sacs from Patients with Lacrimal Duct Obstruction

Introduction Fibrosis is one of the factors contributing to the development of primary acquired lacrimal duct obstruction (LDO). LIGHT (homologous to lymphotoxins, exhibiting inducible expression and competing with herpes simplex virus glycoprotein D for herpes virus entry mediator [HVEM]), a receptor expressed by T lymphocytes, has recently emerged as a new regulator of connective tissue remodeling and fibrotic response. The purpose of this study was to evaluate the role of LIGHT in the pathogenesis of LDO through: (1) assessment of expression of LIGHT and its two receptors, HVEM and LT beta R (lymphotoxin beta receptor), and (2) investigation of potential relationships between expression of LIGHT and its receptors and clinical and histopathologic features. Methods Lacrimal sacs of 30 patients undergoing endoscopic dacryocystorhinostomy because of LDO were assessed intraoperatively and histopathologically with respect to inflammation and fibrosis. Expression of LIGHT, HVEM and LT beta R was assessed by immunohistochemistry using specific antibodies and evaluated semiquantitatively using a four-grade scoring system. Results All investigated molecules, LIGHT/TNFSF14, HVEM and LT beta R, were expressed in biopsies from all patients. The most prominent expression was seen within inflammatory infiltrates. Expression of LIGH, HVEM and LT beta R correlated significantly with the intensity of fibrosis and duration of the disease. In multivariate analysis only LIGHT showed a significant relationship with fibrosis (beta coefficient = 0.759, p = 0.02). There was no significant correlation between expression of any molecule and other demographic or clinical features. Conclusion We assume that LIGHT along with its receptors may be a factor contributing to fibrosis and synechiae formation in the lacrimal sac. This assumption needs to be proven in a future study in a group of patients who fail to improve after the first operation.

Automated summary

The expression of LIGHT and its receptors, HVEM and LT beta R, in lacrimal sac biopsies was significantly correlated with the intensity of fibrosis and disease duration. Only LIGHT showed a significant relationship with fibrosis in multivariate analysis, suggesting a potential role in fibrosis and synechiae formation in the lacrimal sac.