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

Abstract

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 LTβR (lymphotoxin β 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 LTβR was assessed by immunohistochemistry using specific antibodies and evaluated semiquantitatively using a four-grade scoring system. Results All investigated molecules, LIGHT/TNFSF14, HVEM and LTβR, were expressed in biopsies from all patients. The most prominent expression was seen within inflammatory infiltrates. Expression of LIGH, HVEM and LTβR correlated significantly with the intensity of fibrosis and duration of the disease. In multivariate analysis only LIGHT showed a significant relationship with fibrosis ( β 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.

Efficacy of Endoscopic Endonasal Common Canaliculorhinostomy for Chronic Dacryocystitis with Small Lacrimal Sac in the Treatment of Failed Patients After EE-DCR

“…For the patients who have undergone DCR and nally closed the ostium, on the one hand, the mucosa of the surgery area is different from that of normal patients who have not been operated, on the other hand, such patients can be classi ed into the category of recurrent constitution. As we all know, the formation of a perfect ostium requires the joint action of mucosa and bone [11,18]. Studies have pointed out that when the bone pore is too small or the bone window is low during EE-DCR, the Rosenmüller valve is not exposed, resulting in insu cient ostium space.…”

“…It is also reported that rhinostomy ostium incision can be performed to reopen the closed ostium and its curative effect is not very impressive [16]. The study found that in the failures after EE-DCR due to rhinostomy ostium atresia, the residual lacrimal sac of most patients is very small, which adds a considerable obstacle to the success of EE-DCR again [17][18]. The key to the success of EE-DCR lies in the "valve valve anastomosis" between the lacrimal sac valve and the nasal mucosa valve, so as to improve the healing and epithelization of the ostium.…”

TNF superfamily control of tissue remodeling and fibrosis

“…LIGHT has also been shown to play a significant role in connective tissue remodeling in primary acquired lacrimal duct obstruction (LDO), an idiopathic disease most common in the elderly. Bielecki et al found that LIGHT and its receptors, HVEM and LTbR, are expressed on mononuclear cell infiltrates, endothelial cells, fibroblasts, and columnar epithelial cells of the lacrimal sacs (61). Notably, expression of LIGHT, HVEM, and LTbR were significantly correlated with fibrosis severity in the lacrimal sac walls.…”

“…Bielecki et al. found that LIGHT and its receptors, HVEM and LTβR, are expressed on mononuclear cell infiltrates, endothelial cells, fibroblasts, and columnar epithelial cells of the lacrimal sacs ( 61 ). Notably, expression of LIGHT, HVEM, and LTβR were significantly correlated with fibrosis severity in the lacrimal sac walls.…”