Project description:Pterygium is an ocular surface disease that can cause visual impairment if it progressively invades the cornea. Although many pieces of research showed that ultraviolet radiation triggers pterygium pathological progress, the underlying mechanism in pterygium remains indistinct. In this study, we used microarray to evaluate the changes of transcripts between primary pterygium and adjacent normal conjunctiva samples in China, hoping to find underlying pathways involved in pterygium progression.
Project description:Pterygium, abnormal growths of conjunctival tissue onto the cornea, are common ocular surface conditions with a high risk of recurrence after surgery and potential ophthalmic complications. The exact cause of pterygium remains unclear, and the triggers are still unknown. In this study, we investigate the epigenetic profiles of patients with pterygium, focusing on histone H3 lysine 4 (H3K4) and lysine 9 (H3K9) trimethylation (me3). While H3K4me3 levels showed no significant genome-wide change, they were significantly altered in genes related to development and ocular diseases. Conversely, H3K9me3 levels were markedly elevated genome-wide, particularly at the promoters of 82 genes involved in developmental pathways. Furthermore, we identify six genes, ANK2, AOAH, CBLN2, CDH8, CNTNAP4, and DPP6, with decreased gene expression correlated with substantially increased H3K9me3, suggesting their potential as biomarkers for pterygium. This study represents the first report linking histone modification to pterygium progression, providing valuable insights into therapeutic strategies and potential drug targets.
Project description:Pterygium is a highly prevalent, progressive conjunctival eye disease and is characterized by wing-shaped conjunctival fibrovascular overgrowth. Persistent sunlight exposure is a causative factor for this ocular surface disease and mostly affects people working outdoors. Surgical excision remains the only treatment option. Ultraviolet (UV) radiation from sunlight is widely recognized as the primary cause of pterygium. While chronic UV exposure induces epigenetic changes in the skin and contributes to skin cancer, the role of epigenetic alterations in pterygium pathogenesis remains largely unexplored. This study aimed to investigate genome-wide methylation changes in pterygium using the Illumina Infinium Epic v2.0 Methylation array. We identified 1,052 hypermethylated CpGs (499 genes) and 686 hypomethylated CpGs (340 genes) in pterygium tissue compared to control conjunctival tissue from cataract patients (Δβ>|0.1|, P<0.05). Hypomethylated genes were mainly associated with the PI3K-Akt and MAPK pathways, while hypermethylated genes were enriched in pathways related to oxidative stress, autophagy, DNA repair, and Wnt signaling inhibition. These findings suggest that dysregulated DNA methylation may contribute to pterygium pathogenesis by upregulating genes involved in cell proliferation, survival, angiogenesis, fibrosis, and extracellular matrix remodeling, while silencing genes associated with oxidative stress response, autophagy, and DNA damage repair.
Project description:Differential expression comparing active pterygium with atrophic pterygium using data generated from the Brazilian cohort identified differentially expressed genes between the two forms of presentation of this condition
Project description:Pterygium is an ocular surface disorder with high prevalence that can lead to vision impairment. As a pathological outgrowth of conjunctiva, pterygium involves neovascularization and chronic inflammation, but its pathogenesis remains largely unknown. Over the last decade, various types of disease models have been built to study pterygium. Here, we developed a 3D multicellular in vitro pterygium model using the digital light processing (DLP)-based 3D bioprinting of human conjunctival stem cells (hCjSCs). A novel feeder-free culture system was adopted and efficiently expanded the primary hCjSCs with homogeneity, stemness and differentiation potency. The DLP-based 3D bioprinting was able to fabricate hydrogel scaffolds that support the viability and biological integrity of the encapsulated hCjSCs. The bioprinted 3D pterygium model was fabricated with hCjSCs, immune cells and vascular cells to recapitulate the disease microenvironment. Transcriptomic analysis using RNA sequencing (RNA-seq) identified a distinct profile correlated to inflammation response, angiogenesis, and epithelial mesenchymal transition in the bioprinted 3D pterygium model. In addition, the pterygium signatures and disease relevance of the bioprinted model were validated with the public RNA-seq data from patient-derived pterygium tissues. By integrating the stem cell technology and 3D bioprinting, this is the first reported 3D in vitro disease model for pterygium that can be utilized by future studies towards the personalized medicine and the drug screening.
Project description:Comparison of endogenous gene expression differences between pterygium and conjunctiva tissues RNA from donor-matched pterygium and conjunctiva tissues obtained from four patients were evaluated for differences in gene expression