Research progress in animal models of dry eye disease: Types, mechanisms, and application prospects

Dry eye disease (DED) is a prevalent and complex multifactorial ocular surface disorder, leading to significant visual discomfort and diminished quality of life. Animal models are indispensable tools for investigating DED pathology and evaluating therapeutic interventions. This review aims to systematically summarize the primary types of animal models of DED, detail their establishment methods and pathophysiological features, explore their value in elucidating key mechanisms, critically assess their strengths and limitations, and discuss their application prospects. A comprehensive literature search was conducted in electronic databases, including PubMed, Web of Science, and Google Scholar, with a primary focus on literature published within the past decade. Diverse animal models successfully replicate core features of different DED subtypes. Aqueous-deficient models (e.g., surgical excision, scopolamine) mimic tear volume reduction and lacrimal gland inflammation. Evaporative models (e.g., desiccating stress, benzalkonium chloride) effectively simulate tear film lipid layer dysfunction and increased evaporation. Neurogenic models reveal the critical role of neural regulation and neuroinflammation, whereas multifactorial models (e.g., autoimmune, environment-drug combinations) offer high clinical relevance by integrating multiple pathogenic factors. These models have been instrumental in identifying key inflammatory signaling pathways (e.g., NF-κB), immune cell infiltration dynamics, and corneal nerve morphological and functional changes. Animal models are crucial for advancing our understanding of DED pathogenesis and developing novel therapies. The rational selection and application of appropriate models, based on research objectives, are paramount for enhancing translational relevance. These efforts are essential for bridging the translational gap between preclinical research and clinical application.