Abstract
Pterygium is a common ocular disease characterized by proliferating fibrovascular tissue. Pyroptosis, a recently discovered programed cell death, is known to be associated with oxidative stress, one of the main causes of pterygia. Here, we aimed to study the role of pyroptosis in pterygium pathogenesis. The expression of nod-like receptor pyrins-3 (NLRP3), caspase-1, IL-18, and IL-1β was analyzed in 60 human pterygium tissues and 60 human conjunctival epithelium tissues using real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot analysis. Human conjunctival epithelial cells (HConECs) and human pterygium fibroblasts (HPFs) were primary cultured and the level of pyroptosis-associated factors was detected. Both cells were treated with H2O2, and cell lysis was detected by lactate dehydrogenase (LDH) release assay, the expression of the factors by qRT-PCR, Western blot analysis, and immunostaining. The downstream factors IL-18 and IL-1β were measured after inhibition of caspase-1 to confirm the caspase-1-dependent pyroptosis. α-SMA and E-cadherin were detected as indicators of pyroptosis-induced myofibroblast activation in HPFs. We discovered that the expression of the factors was significantly increased in pterygium and that caspase-1-dependent pyroptosis presents in both H2O2-treated HPFs and HConECs during which the expression of these factors was significantly elevated and the elevation of downstream factors IL-18 and IL-1β was restrained after caspase-1 inhibition. α-SMA increase and E-cadherin down-regulation were detected in H2O2-treated HPFs and the changes were reversed by caspase-1 inhibition. Pyroptosis displays a role in the pathological process of pterygium formation and progression. Pyroptosis appears to be an intriguing target to prevent pterygium pathogenesis.
Highlights
Pterygium is an ocular surface disorder characterized as a wing-like shape on the nasal limbus, which hinders vision, causes inflammation, and affects cosmetic appearance.Limbal stem cell degeneration and dissolution of Bowman’s membrane occur in the histopathology of pterygium formation, accompanied by activated fibroblast growth, neovascularization, excessive proliferation of extracellular matrix, and inflammation [1].Surgery is still the main treatment for pterygia, it has a high risk of surgical complications such as recurrence, graft necrosis, and granuloma formation [2]
H2O2 was purchased from Shanghai Zhongshi Chemistry Industry Co (Shanghai, China); Cell Counting Kit-8 was purchased from Dojindo Laboratories (Shanghai, China), and CytoTox 96 Cytotoxicity Assay from Promega Corporation (U.S.A.); caspase-1 inhibitor Ac-YVAD-cmk was purchased from Cayman Chemical (U.S.A.); TRIzol kit and PCR primers were purchased from Invitrogen (Carlsbad, CA); the concentration of RNA was detected by a NanoDrop Spectrophotometer (NanoDrop Technologies, Wilmington, DE)
By validating the elevated pyroptosis-related factors in pterygium tissues and human pterygium fibroblast (HPF), we deducted the possible role of pyroptosis in pterygium pathogenesis
Summary
Pterygium is an ocular surface disorder characterized as a wing-like shape on the nasal limbus, which hinders vision, causes inflammation, and affects cosmetic appearance.Limbal stem cell degeneration and dissolution of Bowman’s membrane occur in the histopathology of pterygium formation, accompanied by activated fibroblast growth, neovascularization, excessive proliferation of extracellular matrix, and inflammation [1].Surgery is still the main treatment for pterygia, it has a high risk of surgical complications such as recurrence, graft necrosis, and granuloma formation [2]. Limbal stem cell degeneration and dissolution of Bowman’s membrane occur in the histopathology of pterygium formation, accompanied by activated fibroblast growth, neovascularization, excessive proliferation of extracellular matrix, and inflammation [1]. Understanding the mechanism of pterygium formation is of vital importance in improving treatment and decreasing occurrence rate. Multiple pathogenic factors, including UV light exposure [4], virus infection [5], oxidative stress [6], fibrosis, and cell epithelial–mesenchymal transition [5], inflammation cascade [7,8], apoptosis [9], extracellular matrix modulators [10], DNA methylation [11], angiogenic, and lymphangiogenic stimulation [12,13], have been proposed, yet the exact mechanisms of pterygium formation have not been elucidated
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