A New Rabbit Model of Chronic Dry Eye Disease Induced by Complete Surgical Dacryoadenectomy

Abstract

ABSTRACTPurpose/Aim: Dry eye disease (DED), common and suboptimally treated, is in need of novel animal models to understand its pathophysiology and assess the efficacy and other parameters of new pharmacological agents for its treatment. The more than 10 rabbit models of DED described to date have significant limitations including induction of mild disease, lack of consistency, and off-target effects when chemical agents are used for disease induction. Our aim was to develop a new model of chronic DED in rabbits that overcomes the limitations of existing models.Materials and Methods: We performed a complete surgical resection of all orbital lacrimal glands (LGs; dacryoadenectomy) in normal adult New Zealand White rabbits. One week after removal of the nictitating membrane, we surgically removed the orbital superior LG, followed by removal of the palpebral superior LG, and finally removal of the inferior LG. Surgery was performed under anesthesia, required about 1 h/eye, and was well-tolerated.Results: Dacryoadenectomy induced severe DED, evidenced by >90% reduction in the tear break up time test, 50% reduction in the Schirmer tear test, 10% increase in tear osmolarity, and a marked increase in the rose bengal staining score. DED was sustained and essentially unchanged for the eight weeks of observation. Sham-operated rabbits showed no such changes, with the exception of a non-significant and transient reduction in the tear break up time test, a response to ocular surgery.Conclusions: This model of stable, chronic, predominantly aqueous-deficient DED recapitulates key clinical and histological features of human DED and is suitable for the study of ocular surface homeostasis, of the pathophysiology of DED, and of the efficacy of candidate drugs for DED treatment.