Rabbit models of dry eye disease: Current understanding and unmet needs for translational research

Dry eye disease (DED) is emerging as an eye health pandemic, affecting millions worldwide. The development of novel drugs, drug delivery systems, and targeted therapies for addressing the inflammation in DED necessitates progress in experimental models of DED. Animal models of DED have been created for simulating the two clinically described forms of DED: lacrimal insufficiency and the evaporative DED models. Although most DED models have relied upon rodents, the larger eye size and longer life span of rabbits and the closer resemblance to human lacrimal glands, render rabbits a promising near-ideal model for studying DED. Since the first rabbit DED model was described, numerous modifications including the use of topical epitheliotoxic drugs, neural abolition, activated lymphocytes injection, and surgical dacryoadenectomy have been introduced. The stability of these models, whether short-term or long-term, accordingly guides their experimental or therapeutic utility. A rabbit autoimmune dacryoadenitis model has successfully simulated DED signs and features of lacrimal gland inflammation, as observed in Sjogren's syndrome, that improved with mesenchymal stem cell therapy. This review summarizes the comparative microscopic anatomy of rabbit and human lacrimal glands, various existing rabbit DED models and their respective suitability for understanding pathogenetic mechanism of DED or for experimental drug testing. Also, the insights gained from animal models in dry eye management is described along with the future perspectives. There is still a pressing need of developing rabbit models for studying the pathogenesis of complex ocular surface changes in evaporative and aqueous deficiency DED other than autoimmune dacryoadenitis.