Emerging RNA-Based Therapeutic Strategies for Inflammatory Ophthalmic Disorders of the Anterior Segment: Mechanistic Insights and Translational Potential

Abstract

Anterior segment ocular inflammatory disorders, including conjunctivitis, keratitis, scleritis, dry eye disease, and anterior uveitis, represent a major cause of visual impairment worldwide. Conventional pharmacological therapies such as antihistamines, corticosteroids, and immunomodulators primarily provide symptomatic relief but are limited by their adverse effects, poor long-term efficacy, and lack of disease-modifying potential. In this review, RNA-based therapeutics are discussed in detail, emerging as promising and targeted approaches for modulating the molecular mechanisms underlying ocular anterior segment inflammatory conditions. These strategies include small interfering RNA (siRNA), short hairpin RNA (shRNA), antisense oligonucleotides (ASOs), messenger RNA (mRNA), microRNA (miRNA), and long noncoding RNA (lncRNA), each offering distinct mechanisms to regulate gene expression and inflammatory signaling pathways. RNA therapeutics enable precise silencing or modulation of key mediators such as cytokines, transcription factors, and immune regulators involved in Th2-driven and immune-mediated inflammatory responses. Recent advances in nanotechnology-based delivery systems, including lipid nanoparticles, polymeric carriers, and viral vectors, have significantly improved RNA stability, bioavailability, and targeted ocular delivery. Despite these advances, challenges such as ocular surface barriers, rapid tear clearance, enzymatic degradation, off-target effects, and potential immunogenicity remain significant hurdles. Overall, RNA-based therapies hold substantial potential as next-generation, disease-modifying treatments for anterior segment inflammatory disorders, including DED, warranting further translational and clinical investigation.