Abstract
To evaluate the effect of 0.2% ambroxol eye drop on tear secretion and corneal healing on a rabbit dry eye model, and to delineate potential underlying mechanisms. A mixed mechanism dry eye model was created using 12 healthy New Zealand rabbits by excision of the main lacrimal glands, Harderian gland and nictitating membrane. Establishment of the model was confirmed by the decrease of Schirmer I and increase of corneal fluorescein staining scores. Two weeks after model creation, the rabbits were randomly and evenly divided into NaCl, 0.1% sodium hyaluronate and 0.2% ambroxol groups. Each group was administered the respective eye drops 4 times a day for four weeks. The Schirmer I test and corneal fluorescein staining were performed at two and four weeks. After four weeks of treatment, the animals were sacrificed and the conjunctiva and eyelid specimens collected. Inflammatory factors IL-8, TNF-α, and goblet cell specific mucin MUC5AC were measured by ELISA while the lid meibomian gland was evaluated by oil red O staining. Compared with the baseline, 2 weeks after the surgery, Schirmer I test value decreased significantly (20.35 ± 5.18 mm/5 min vs 13.95 ± 4.64 mm/5 min, p < 0.01), and the fluorescein staining score increased significantly (0.5 ± 0.6 vs 5.5 ± 1.4, p < 0.01). After four weeks of treatment, compared with the NaCl and sodium hyaluronate groups, tear secretion in ambroxol group increased significantly (p < 0.01), while the corneal fluorescence staining score decreased significantly (p < 0.01). In the conjunctival tissue, significant decrease was seen in TNF-α (p < 0.01) and IL-8 [p (unilateral) < 0.05] concentrations in ambroxol group, and significant increase in MUC5AC concentration (p < 0.01) in ambroxol group as well. The lipid content in the lid meibomian glands appeared increased after the administration of ambroxol. The present rabbit dry eye model study demonstrated potentials of topically administered 0.2% ambroxol in stimulating tear and mucin secretion, inhibiting ocular surface inflammation, promoting corneal healing, and possibly augmenting meibomian gland lipid production.
Highlights
Altered tear film (TF) composition is a common cause of dry eye disease (DED) which can further lead to ocular surface inflammation and loss of tear homeostasis
The decreased tear secretion by about 30% and increased corneal staining on the epithelium confirmed the establishment of the rabbit dry eye model
Compared to two weeks after the surgeries, statistically significant increase in tear secretion in the ambroxol group was seen at four weeks after treatment (p < 0.01)
Summary
Altered tear film (TF) composition is a common cause of dry eye disease (DED) which can further lead to ocular surface inflammation and loss of tear homeostasis. There are two types of DED in current classification— aqueousdeficient and evaporative, related directly to decrease in aqueous or lipid components of TF [1]. Evaporative DED is more common than aqueous-deficient type, but more than one-third of patients will have a combination of both. DED represents one of the biggest unmet needs in ophthalmology. Current methods can often alleviate but not cure DED. In-depth study of the pathogenesis of DED, as well as the discovery of new drugs are still vitally important
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