Systems biology of dry eye: Unraveling molecular mechanisms through multi-omics integration

Dry eye disease (DED) is a multifactorial condition with complex and incompletely understood molecular mechanisms. Advances in multi-omics technologies, including genomics, transcriptomics, proteomics, metabolomics, and microbiomics, have provided new insights into the pathophysiology of DED. Genomic analyses have identified key genetic variants linked to immune regulation and lacrimal gland function. Transcriptomic studies reveal upregulated inflammatory pathways in ocular surface tissues, implicating these as core drivers of chronic inflammation. Proteomic research highlights significant alterations in tear protein composition, especially proteins involved in inflammation and tissue repair. Metabolomics studies focus on disrupted lipid metabolism and oxidative stress, which are crucial in maintaining tear film stability. Furthermore, microbiome research has demonstrated reduced microbial diversity and increased pathogenic bacteria, exacerbating inflammatory responses. The integration of multi-omics data allows for the identification of novel biomarkers and therapeutic targets, enabling precision diagnostics and personalized treatments. Therefore, this review highlights the critical importance of multi-omics approaches in deepening our understanding of DED's complex molecular mechanisms and their potential to transform clinical management and therapeutic innovations in this challenging field.