The Roles Of Cell-Matrix Interaction In Cellular Dysfunction During Pterygium Progression

Although the phenotype of pterygium has known as high levels of proliferation, inflammation,angiogenesis, and extensive amount of extracellular matrix accumulation, the specific molecular mechanism of pterygium pathogenesis is still unclear. Cells can mechanosense the mechanical properties of their microenvironment and convert them into chemical signals to regulate various cellular functions such as proliferation, apoptosis, differentiation and migration, known as mechanotransduction. We aim to understand the underlying molecular mechanism of pterygium pathogenesis.

Department of Ophthalmology, Soonchunhyang University College of Medicine, Soonchunhyang University Seoul Hospital, Seoul, Republic of Korea. Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, Cheonan-si, Republic of Korea

Transcriptome analyses using human pterygium epithelial cells and fibroblasts isolated from primary pterygium tissue. Quantitative polymerase chain reaction (PCR) and wound scratch test were performed to compare characteristics between pterygial and normal conjunctival cells. Traction force microscope (TFM) analysis and migration ability in different matrix stiffness conditions (matrix stiffnesses to mimic normal (~2.5 kPa) and pterygial (~60 kPa) tissue) were compared between pterygial and normal conjunctival cells.

Transcriptome profiles showed significantly upregulated cell adhesion and migration-associated signaling pathways were in the pterygial cells and which were validated by qPCR (MMP, integrin alpha) and wound scratch assays. TFM analyses revealed that pterygium cells showed significantly higher levels of mechano-sensitiveness to their microenvironment and underwent mechanotransduction. Cells cultured on a stiff matrix exhibited increased growth, elongation, and numbers of vinculin, and furthermore, the same cell behaviors were significantly increased in both pterygium-derived cells.

These results indicate both pterygium-derived fibroblasts and epithelial cells are much sensitive to the mechanical properties of their microenvironment suggesting that fibrotic nature of pterygium tissues could play a significant role in regulation of pterygium cell migration and pathogenesis. These findings may offer insight into the important roles of cell-matrix interactions in pterygium pathophysiology, which could provide a valid tool to develop potential therapeutic candidates.