Li Yu1,2,3, Dhruva Bhattacharya4, Zhenhan Wang5, Mingwu Wang6,7. 1. Shenzhen Key Laboratory of Ophthalmology, Jinan University Shenzhen Eye Hospital, Shenzhen, Guangdong, People's Republic of China. 2. Shenzhen Ocular Trauma and Stem Cell Differentiation Service, Shenzhen, Guangdong, People's Republic of China. 3. Shenzhen University College of Optometry, Shenzhen, Guangdong, People's Republic of China. 4. Department of Ophthalmology and Vision Science, University of Arizona College of Medicine, Tucson, AZ, USA. 5. Shenzhen Tusang Medical Science Corp. Ltd., Shenzhen, Guangdong, People's Republic of China. 6. Department of Ophthalmology and Vision Science, University of Arizona College of Medicine, Tucson, AZ, USA. mingwuwang@hotmail.com. 7. NeuVision Medical Institute, Tucson, AZ, USA. mingwuwang@hotmail.com.
Abstract
PURPOSE: To investigate if topical administration of ambroxol promotes tear secretion and to compare with Diquas ophthalmic eye drop. METHODS: Two consecutive studies were conducted using sixteen (32 eyes) New Zealand White rabbits. The first study compared the efficacy of ambroxol hydrochloride (0.05%, 0.2%, and 1.0%) on tear and mucin secretion when administered twice daily. Tear secretion was assessed by Schirmer test I and mucin production by conjunctival impression cytology and PAS stain. The second study compared 0.2% ambroxol hydrochloride with Diquas. A human goblet cell line and human conjunctival tissue were used to test the effect of ambroxol hydrochloride on the expression of aquaporin 5 (AQP5) and MUC5AC, using reverse transcriptase-quantitative polymerase chain reaction and immunoblotting. RESULTS: All three concentrations of ambroxol hydrochloride demonstrated significant efficacy on tear stimulation within 2 weeks of treatment and total mucin component appeared increased. When administered topically twice daily, 0.2% ambroxol hydrochloride was more effective in augmenting tear secretion than Diquas. With 24 h of treatment, 5 μM of ambroxol hydrochloride upregulated AQP5 and MU5AC mRNA and MUC5AC protein in a goblet cell line. When tested on preserved human conjunctiva tissue, a trend of increased production of MUC5AC protein was seen (P = 0.26). CONCLUSION: Ambroxol is effective in augmenting tear secretion at the ocular surface in rabbits. With actions desirable of a candidate dry eye drug, further investigation of ambroxol and related compounds is warranted to explore their value toward clinical application.
PURPOSE: To investigate if topical administration of ambroxol promotes tear secretion and to compare with Diquas ophthalmic eye drop. METHODS: Two consecutive studies were conducted using sixteen (32 eyes) New Zealand White rabbits. The first study compared the efficacy of ambroxol hydrochloride (0.05%, 0.2%, and 1.0%) on tear and mucin secretion when administered twice daily. Tear secretion was assessed by Schirmer test I and mucin production by conjunctival impression cytology and PAS stain. The second study compared 0.2% ambroxol hydrochloride with Diquas. A human goblet cell line and human conjunctival tissue were used to test the effect of ambroxol hydrochloride on the expression of aquaporin 5 (AQP5) and MUC5AC, using reverse transcriptase-quantitative polymerase chain reaction and immunoblotting. RESULTS: All three concentrations of ambroxol hydrochloride demonstrated significant efficacy on tear stimulation within 2 weeks of treatment and total mucin component appeared increased. When administered topically twice daily, 0.2% ambroxol hydrochloride was more effective in augmenting tear secretion than Diquas. With 24 h of treatment, 5 μM of ambroxol hydrochloride upregulated AQP5 and MU5AC mRNA and MUC5AC protein in a goblet cell line. When tested on preserved human conjunctiva tissue, a trend of increased production of MUC5AC protein was seen (P = 0.26). CONCLUSION:Ambroxol is effective in augmenting tear secretion at the ocular surface in rabbits. With actions desirable of a candidate dry eye drug, further investigation of ambroxol and related compounds is warranted to explore their value toward clinical application.
Authors: Jennifer P Craig; J Daniel Nelson; Dimitri T Azar; Carlos Belmonte; Anthony J Bron; Sunil K Chauhan; Cintia S de Paiva; José A P Gomes; Katherine M Hammitt; Lyndon Jones; Jason J Nichols; Kelly K Nichols; Gary D Novack; Fiona J Stapleton; Mark D P Willcox; James S Wolffsohn; David A Sullivan Journal: Ocul Surf Date: 2017-08-08 Impact factor: 5.033
Authors: William R Thelin; M Ross Johnson; Andrew J Hirsh; Claire L Kublin; Driss Zoukhri Journal: J Ocul Pharmacol Ther Date: 2012-03-28 Impact factor: 2.671