Application of Animal Models in Interpreting Dry Eye Disease

Abstract

Different pathophysiologic mechanisms are involved in the initiation, development, and outcome of dry eye disease (DED). Animal models have proven valuable and efficient in establishing ocular surface microenvironments that mimic humans, thus enabling better understanding of the pathogenesis. Several dry eye animal models, including lacrimal secretion insufficiency, evaporation, neuronal dysfunction, and environmental stress models, are related to different etiological factors. Other models may be categorized as having a multifactorial DED. In addition, there are variations in the methodological classification, including surgical lacrimal gland removal, drug-induced models, irradiation impairment, autoimmune antibody-induced models, and transgenic animals. The aforementioned models may manifest varying degrees of severity or specific pathophysiological mechanisms that contribute to the complexity of DED. This review aimed to summarize various dry eye animal models and evaluate their respective characteristics to improve our understanding of the underlying mechanism and identify therapeutic prospects for clinical purposes.

Keywords: DED; animal model; dry eye; environmental stress; evaporative; lacrimal gland; tear deficiency; translational research.

Figure 1

Principles for animal dry eye modeling. A schematic showing approaches to developing animal dry eye models, including major methods used in recently published studies, as described in this review. Lacrimal glands excision, neural pathway blocking, and autoimmune disease models, including Sjögren's syndrome and systemic lupus erythematosus, have been developed by targeting the lacrimal gland. These result in an aqueous deficiency in the tear film. Conjunctival goblet cell damage can result in mucin deficiency in the tear film. Further, chemicals, drugs, and radiation hazards mainly cause corneal epithelium damage. Some gene-modified mice can present with dysfunction or direct damage of the Meibomian glands, resulting in lipid deficiency in the tear film. Environmental stress due to changing humidity, controlling airflow, and/or introduction of air pollution particulate matter, could also be significant in animal dry eye modeling.