Molecular Basis of Pterygium Development

Abstract

Pterygium pathogenesis is mainly related to UV light exposure. However, the exact mechanisms by which it is formed have not been elucidated. Clinical advances in surgical treatment use conjunctival autografts and amniotic membranes in combination with adjuvant therapies, including mitomycin C, β-radiation, and 5-fluoroacil, to reduce recurrence. Several studies aim to unveil the molecular mechanisms underlying pterygium growth and proliferation. They demonstrate the role of different factors, such as viruses, oxidative stress, DNA methylation, apoptotic and oncogenic proteins, loss of heterozygosity, microsatellite instability, inflammatory mediators, extracellular matrix modulators, lymphangiogenesis, cell epithelial-mesenchymal transition, and alterations in cholesterol metabolism in pterygium development. Understanding the molecular basis of pterygium provides new potential therapeutic targets for its prevention and elimination. This review focuses on providing a broad overview of what is currently known regarding molecular mechanisms of pterygium pathogenesis.

Cultivation and characterization of pterygium as an ex vivo study model for disease and therapy

“…Pterygium as a structure consists of a mixture of epithelial and fibroblastic cells, proliferation of which closely determines its recurrence and severity [6]. The stratified outgrowing cell model for pterygium expansion ex vivo shown here has the advantage of giving immediate adherence of the graft to the cell culture plate (e.g.…”

“…The proliferation marker Ki-67 has been found to be overexpressed in the epithelial cell layer of pterygium rather than in the stromal fibroblasts, in particular, the head and the body parts compared to the healthy conjunctiva. Accordingly, corneal invasion by the pterygium might be associated with proliferation of the epithelium, although it is clear that fibroblasts play important role in epithelial-mesenchymal interactions [6,[20][21][22]. Ki-67 has also been expressed in conjunctival and eyelid tumours [23], the positivity of which was low in the pterygium graft containing cultures, which was additionally five times less expressed in the multi-layered outgrowing tissue.…”

“…It is a sensitive and stable biomarker for DNA damage estimation and has been expressed more in the epithelium of the head of primary pterygium compared to the healthy conjunctiva. While pterygium is considered to be a nonmetastatic lesion with limited local invasion, the presence of 8-OHdG could confirm a visible genetic instability which is in contrast to its benign clinical course [6,31].…”

“…Inflammation can induce the angiogenic pathways, which can result in neovascularization and contribute to further pterygium growth. Mitomycin C (MMC), an anti-mitotic agent often used in recurrent pterygium ablation surgery can induce apoptosis of keratocytes and myofibroblasts [6]. Herein, the effect MMC has upon the secretion of pro-inflammatory cytokines, interleukin 6 (IL-6) and IL-8 was checked after repeated pterygium graft cultivation, thus resembling closely its application in vivo for recurrent cases.…”

“…A wide range of alternative pathogenic factors have been proposed, including viral infections, epigenetic aberrations, epithelial-mesenchymal transition, immunologic and anti-apoptotic mechanisms, angiogenic and lymphangiogenic stimulation, deregulation of extracellular matrix (ECM) modulators and growth factors, inflammation cascades, recruitment of bone-marrow-derived stem-and progenitor cells, and modifications in the cholesterol metabolism. Most of these factors are rather related to the development and maintenance of the disease than to its origin [6].…”