Linking environmental cadmium to pterygium pathogenesis: Mechanistic insights from fibroblast proliferation and...

Cadmium, a ubiquitous environmental toxicant, poses significant risks to human health, including ocular surface damage. This study investigates the link between cadmium exposure and pterygium, a common ocular fibrovascular proliferative disorder, using human conjunctival fibroblasts (HconFs) as an in vitro model. We demonstrated that low-dose cadmium chloride (CdCl₂, 1 μmol/L) significantly enhanced HconFs proliferation and disrupted cell cycle progression by reducing the G₀/G₁ phase population and increasing G₂/M phase entry. Transcriptome analysis identified 724 differentially expressed genes (DEGs), predominantly enriched in metal ion response, detoxification, and mineral absorption pathways. Bioinformatic screening and validation revealed significant upregulation of FGF18, PTPRC, NDP, and MT1X, alongside downregulation of MX1. Critically, FGF18 and MT1X were consistently upregulated in clinical pterygium tissues, suggesting their pivotal role in linking cadmium toxicity to disease pathogenesis. Furthermore, calcium chloride (CaCl₂, 3 mmol/L) co-treatment effectively mitigated cadmium-induced proliferation, supporting a protective role of calcium via competitive inhibition. These findings indicate that cadmium promotes HconFs proliferation by disrupting intracellular metal homeostasis and activating proliferative and fibrotic gene programs, including MT1X and FGF18, via pathways potentially involving ERK/MAPK and Wnt/β-catenin signaling, thereby contributing to pterygium development. This study provides novel insights into environmental etiologies of pterygium and proposes calcium supplementation as a potential preventive strategy against cadmium-related ocular surface disorders.