Transcriptomics and network analysis highlight potential pathways in the pathogenesis of pterygium

Abstract

Pterygium is a common ocular surface condition frequently associated with irritative symptoms. The precise identity of its critical triggers as well as the hierarchical relationship between all the elements involved in the pathogenesis of this disease are not yet elucidated. Meta-analysis of gene expression studies represents a novel strategy capable of identifying key pathogenic mediators and therapeutic targets in complex diseases. Samples from nine patients were collected during surgery after photo documentation and clinical characterization of pterygia. Gene expression experiments were performed using Human Clariom D Assay gene chip. Differential gene expression analysis between active and atrophic pterygia was performed using limma package after adjusting variables by age. In addition, a meta-analysis was performed including recent gene expression studies available at the Gene Expression Omnibus public repository. Two databases including samples from adults with pterygium and controls fulfilled our inclusion criteria. Meta-analysis was performed using the Rank Production algorithm of the RankProd package. Gene set analysis was performed using ClueGO and the transcription factor regulatory network prediction was performed using appropriate bioinformatics tools. Finally, miRNA-mRNA regulatory network was reconstructed using up-regulated genes identified in the gene set analysis from the meta-analysis and their interacting miRNAs from the Brazilian cohort expression data. The meta-analysis identified 154 up-regulated and 58 down-regulated genes. A gene set analysis with the top up-regulated genes evidenced an overrepresentation of pathways associated with remodeling of extracellular matrix. Other pathways represented in the network included formation of cornified envelopes and unsaturated fatty acid metabolic processes. The miRNA-mRNA target prediction network, also reconstructed based on the set of up-regulated genes presented in the gene ontology and biological pathways network, showed that 17 target genes were negatively correlated with their interacting miRNAs from the Brazilian cohort expression data. Once again, the main identified cluster involved extracellular matrix remodeling mechanisms, while the second cluster involved formation of cornified envelope, establishment of skin barrier and unsaturated fatty acid metabolic process. 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. Our results reveal differentially expressed genes not only in pterygium, but also in active pterygium when compared to the atrophic ones. New insights in relation to pterygium’s pathophysiology are suggested.

Synergic Action of Insulin-like Growth Factor-2 and miRNA-483 in Pterygium Pathogenesis

“…Notably, pterygium is referred to as an "ophthalmic enigma" [4] because it represents a multifactorial disease as a result of a multitude of risk factors, including inflammation [5][6][7], antiapoptotic growth and proliferative mechanisms [8,9], angiogenic factors [10,11], oxidative stress and hypoxic ischemic injuries [12,13], viral infections [14], and extracellular matrix remodeling [15]. However, there is scientific consensus in the perception of pterygium as one of the most common sun-related eye diseases (ophthalmohelioses) [16], with UV-B playing a key role through inducing oxidative stress and is responsible for phototoxic DNA damage [17,18].…”

Integrative analysis of ex vivo studies and microarray reveals the novel inhibitor effects of trehalose on the pathogenesis of pterygium

“…Despite today's technological conditions, research into the development of effective drugs for pterygia is progressing at a slower pace because the formation of pterygia is highly complicated. Its complete etiology is still unknown (De Guimarães et al., 2022; Liu et al., 2023) Using microarray or high‐throughput sequencing technology, previous studies have demonstrated that mRNA, miRNA, and lncRNA dysregulation is mainly associated with extracellular matrix organization, blood vessel morphogenesis, and focal adhesion (De Guimarães et al., 2022).…”

Resveratrol inhibits TGF-β1–induced fibrotic effects in human pterygium fibroblasts

“…Pterygium is a fibrovascular degenerations of the conjunctiva that extends into the corneal limbus [ 1 ]. It can cause significant damage to visual function, triggering irritation [ 2 ], inflammation [ 3 ] and astigmatism [ 4 ]. Currently, there is no effective drug or conservative treatment for advanced pterygium, and surgery remains the best treatment option.…”