Expression patterns of conjunctival mucin 5AC and aquaporin 5 in response to acute dry eye stress

Bhattacharya, Dhruva; Yu, Li; Wang, Ming-Wu

doi:10.1371/journal.pone.0187188

Cited by 16 publications

(12 citation statements)

References 66 publications

(86 reference statements)

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“…Our earlier research suggested that augmentation of the AQP function in the conjunctiva has the potential to promote the secretion of tear and MUC5AC, the gel-forming mucin secreted by goblet cells [2,11]. As an active agent on the ocular surface, MUC5AC can help evenly disperse the aqueous layer of the TF [18].…”

Section: Discussionmentioning

confidence: 99%

“…The natural hydrophobicity of cell membrane lipids requires mucin to fix the tear film on the ocular surface for lubrication and protection. Our early study found that transconjunctival fluid transport driven by osmotic pressure gradient is mainly carried out through aquaporin, and its in-creased expression can drive the expression and secretion of MUC5AC, the most important gel-forming mucin in tears, from conjunctival epithelial goblet cells [2]. We have also recently discovered that ambroxol can stimulate the expression of aquaporin 5 (AQP5) and mucin 5AC (MUC5AC) in vitro, and can promote tear secretion in normal rabbits [3], demonstrating potential as a drug for DED.…”

Section: Introductionmentioning

confidence: 99%

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An animal study on the effect of topically administered ambroxol for dry eye

Wang¹,

Yu²,

Zhang³

et al. 2022

Front. Biosci. (Landmark Ed)

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

An animal study on the effect of topically administered ambroxol for dry eye

Wang¹,

Yu²,

Zhang³

et al. 2022

Front. Biosci. (Landmark Ed)

Self Cite

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“…Danjo et al detected an alteration of the distribution of mucin in patients with DES [ 65 ]. Furthermore, the association of reduced levels of Muc5AC and DES is reported in clinical and experimental studies [ 66 , 67 , 68 , 69 ]. In the current study, we found decreased levels of Muc1, Muc4, and Muc5 on the ocular surface of rats with DES which was significantly restored with LCD administration at both doses.…”

Section: Discussionmentioning

confidence: 99%

A Novel Integrated Active Herbal Formulation Ameliorates Dry Eye Syndrome by Inhibiting Inflammation and Oxidative Stress and Enhancing Glycosylated Phosphoproteins in Rats

et al. 2020

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Dry eye syndrome (DES) is a chronic condition of the eye with insufficient production of tears leading to inadequate lubrication of eyes. Symptoms of DES are associated with discomfort and redness of the eye, blurred vision, and tear film instability which leads to the damaged ocular surface. Inflammation and oxidative stress play a significant role in the pathogenesis of the disease. In this study, the protective effect of different doses (100 or 200 mg/kg) of a novel multi-component oral formulation of lutein/zeaxanthin, curcumin, and vitamin D3 (LCD) was evaluated using a rat model with benzalkonium chloride (BAC)-induced dry eye syndrome. The formulation was administered orally to rats for 4 weeks. We observed a significant improvement in tear volume, tear breakup time, tear film integrity, and reduction in overall inflammation in rats fed with the LCD at dose 200 mg/kg performing better than 100 mg/kg. Furthermore, the formulation helped in lowering oxidative stress by increasing antioxidant levels and restored protective tear protein levels including MUC1, MUC4, and MUC5AC with 200 mg of LCD having the most significant effect. The results strongly suggest that the combination of lutein/zeaxanthin, curcumin, and vitamin-D3 is effective in alleviating the symptoms of dry eye condition with a multi-modal mechanism of action.

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“…In the present study, AQP5 expression was significantly lowered characteristically in DM cases as well as in cases aged � 51 years post -VR surgery compared to pre-surgery. AQP5 highly expressed in lacrimal and salivary gland was reported to be lowered in a rabbit model of dry eye and the interaction between MUC5AC and AQP5 was pointed out [38]. However, in Sjogrens syndrome the tear AQP5 protein is reported to be increased.…”

Section: Dry Eye In Dm Cases Undergoing Vr Surgerymentioning

confidence: 99%

Altered mucins and aquaporins indicate dry eye outcome in patients undergoing Vitreo-retinal surgery

et al. 2020

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Vitreo-retinal (VR) surgeries induce conjunctival changes. However, there are no study reports regarding prevalence and severity of dry eye after these surgeries. This study evaluated dry eye outcome after VR surgery. Patients undergoing VR surgery classified as scleral buckle and microincision vitrectomy surgery (n = 44, mean age: 56.09±10.2 years) were recruited. Dry eye evaluation was done before and 8 weeks after surgery (2 weeks after omitting topical eye drops). Conjunctival imprint cytology for goblet cell count and tear Mucin 5AC (MUC5AC) protein estimation was done. Gene expressions of MUC5AC, MUC4, MUC16, Aquaporin 4 (AQP4) and AQP5 were analyzed in the conjunctival imprint cells by qPCR. None of the patients exhibited clinical signs of dry eye after VR surgery. But the conjunctival goblet cell density (GCD) was significantly lowered post-VR surgery (63% cases, **p = 0.012) with no alterations in the tear MUC5AC protein. Post-VR surgery, the conjunctival cell gene expression of MUC4, MUC16 and AQP4 were significantly increased (*p = 0.025, *p = 0.05 and *p = 0.02 respectively) and AQP5 was significantly lowered (*p = 0.037), with no change in MUC5AC expression. Tear cytokines were significantly increased post-VR surgery (anti-inflammatory: IL1RA, IL4, IL5, IL9, FGF; PDGFbb and pro-inflammatory: IL2, IL6, IL15, GMCSF and IFNg). Though clinical signs of dry eye were not observed after VR surgery, ocular surface changes in the form of reduced GCD, altered MUC5AC, MUC4, MUC16, AQP4, AQP5 and cytokines are suggestive of dry eye outcome at the molecular level especially inpatients aged above 51 years, especially female gender and those who are diabetic.

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Expression patterns of conjunctival mucin 5AC and aquaporin 5 in response to acute dry eye stress

Cited by 16 publications

References 66 publications

An animal study on the effect of topically administered ambroxol for dry eye

An animal study on the effect of topically administered ambroxol for dry eye

A Novel Integrated Active Herbal Formulation Ameliorates Dry Eye Syndrome by Inhibiting Inflammation and Oxidative Stress and Enhancing Glycosylated Phosphoproteins in Rats

Altered mucins and aquaporins indicate dry eye outcome in patients undergoing Vitreo-retinal surgery

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