IMR Press / FBL / Volume 27 / Issue 1 / DOI: 10.31083/j.fbl2701004
Open Access Original Research
An animal study on the effect of topically administered ambroxol for dry eye
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1 Shenzhen Eye Hospital, School of Optometry, Shenzhen University, 518040 Shenzhen, Guangdong, China
2 Shenzhen Tusang Medical Science Corp, 518000 Shenzhen, Guangdong, China
3 Department of Ophthalmology and Vision Science, University of Arizona College of Medicine, Tucson, AZ 85710, USA
4 NeuVision Medical Institute, Tucson, AZ 85718, USA

Academic Editor: Shikun He

Front. Biosci. (Landmark Ed) 2022, 27(1), 4; https://doi.org/10.31083/j.fbl2701004
Submitted: 19 October 2021 | Revised: 18 November 2021 | Accepted: 23 November 2021 | Published: 5 January 2022
(This article belongs to the Special Issue Recent Advances in Eye and Vision Research)
Copyright: © 2022 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.
Abstract

Objective: 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. Materials and method: 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. Results: 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. Conclusion: 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.

Keywords
Ambroxol
Secretagogue
Dry eye disease
Rabbit dry eye model
Inflammatory cytokines
MUC5AC
ICAM-1
Lifitegrast
Figures
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