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

Abstract

Purpose/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 nonsignificant 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.

Chronic dry eye induced corneal hypersensitivity, neuroinflammatory responses, and synaptic plasticity in the mouse trigeminal brainstem

“…Previous preclinical models have been developed to mimic DED using desiccative environment exposure [13, 14], the injection of anticholinergic drugs [15, 16] or botulinum toxin [17], or instillation of benzalkonium chloride [3, 18, 19]. In addition to these models, surgical aqueous tear deficiency models have also been developed in mice, consisting of excision of the extraorbital lacrimal gland (ELG) [20–23], both the extraorbital and intraorbital lacrimal glands [24], or full removal of all orbital lacrimal glands [25]. Another type of surgical model has been developed, consisting of excision of the lacrimal and Harderian glands and nictitating membrane in rabbits [26, 27].…”

Optimization of a Rabbit Dry Eye Model Induced by Topical Instillation of Benzalkonium Chloride

“…Based on the etiology and classification of dry eye, different animal models have been developed over the years [4,5]. In rabbits, dry eye has been induced by many procedures such as dacryoadenectomy [6], female and male castration [7,8], desiccating stress [9], induced autoimmune dacryoadenitis [10], injection of the lacrimal gland with concanavalin A [11], injury of the drainage duct [12], nerve denervation [13], and topical instillation of atropine [14] or benzalkonium chloride (BAC) [15]. e current publication is focused on the topical instillation of BAC.…”

Current treatment modalities for dry eye disease

“…Ранее, в особо тяжелых случаях ССГ с изменениями роговицы ксеротического характера, выполняли такие операции, как пересадка протока околоушной слюнной железы, трансплантация подчелюстной слюнной железы. В настоящее время указанные хирургические вмешательства выполняются довольно редко [45,46]. К операциям, ограничивающим испаряемость слезной жидкости, относятся канторафия (ушивание век с медиального или латерального угла глазной щели) и тарзорафия (полное или частичное сшивание краев век).…”