Integrative Transcriptomic Profiling and Network-Based Analysis Reveal Disease-Specific and Shared Molecular Pathways Across Five Major Ocular Disorders

Ocular diseases constitute a heterogeneous group of conditions that collectively cause significant visual impairment and blindness. Despite advances in clinical diagnostics, the molecular mechanisms driving ocular pathology remain insufficiently understood. This study sought to systematically investigate transcriptional dysregulation across five distinct ocular disorders by integrating multi-cohort gene expression datasets. Five GEO microarray datasets, GSE۱۳۷۹۹۶ (Congenital Aniridia,n=۱۲), GSE۱۷۵۴۹ (Choroideremia, n=۱۴), GSE۱۱۲۲۰۱ (Corneal Dystrophy, n=۲۰), GSE۹۹۴۴ (Glaucoma, n=۱۰), and GSE۲۹۸۰۱ (Macular Degeneration, n=۱۲ ) were processed using a standardized pipeline involving background correction, normalization, and gene-level filtering. Differential expression analysis was performed with Limma, and significance was determined using the Benjamini–Hochberg FDR correction, adjp-value < ۰.۰۵, and logFC threshold (|log₂FC| > ۱). Protein–protein interaction (PPI) networks were constructed using STRING and analyzed in Cytoscape, while GO and KEGG enrichment analyses were conducted using Enrichr. Distinct transcriptional signatures were identified across the five disorders, including ۱۱۲ DEGs in congenital aniridia, ۲۱ in choroideremia, ۸۱۲ in corneal dystrophy, ۳۲ in glaucoma, and ۱۷ in macular degeneration. PPI networks revealed prominent disease-specific functional clusters, including developmental regulation in aniridia, retinal metabolic pathways in choroideremia, inflammatory and extracellular matrix remodeling pathways in corneal dystrophy, neurodegenerative processes in glaucoma, and oxidative stress responses in macular degeneration. Cross-dataset comparisons highlighted shared molecular themes, including immune activation, stress-response signaling, and extracellular matrix dysregulation. This integrative systems-level analysis provides a comprehensive molecular framework for understanding major ocular disorders. The identification of key regulatory hubs, disease-specific pathways, and shared pathogenic mechanisms offers new perspectives for the development of precision biomarkers and targeted therapeutic strategies. These findings enhance the current molecular understanding of ocular disease biology and establish a scalable analytical foundation for future multi-omics investigations.

کلیدواژه ها:

Ocular disease gene expression analysis ، Differentially expressed genes in eye disorders ، Ocular biomarker discovery ، Transcriptomic profiling of ocular diseases ، Molecular pathways in ocular disorders