Effects of Topical Mucolytic Agents on the Tears and Ocular Surface: A Plausible Animal Model of Mucin-Deficient Dry Eye

Li, Xiangzhe; Kang, Boram; Woo, In Ho; Eom, Youngsub; Kim, Hyo Myung; Song, Jong Suk

doi:10.1167/iovs.18-23860

Cited by 18 publications

(11 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NAC is nowadays widely used in clinical work as a mucolytic agent to treat patients with too much sputum ( Li et al, 2018a ). However, it was reported that NAC can promote liver functions in NAFLD patients, and there are a number of clinical trials investigating the effect of NAC in treating metabolic syndromes ( Oliveira et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

“…As a widely applied antioxidant agent, N-acetyl cysteine (NAC) is usually considered as ROS scavenger in basic experimental investigations ( Rushworth and Megson, 2014 ) and is demonstrated to be effective in treating murine diseases such as ischemia/reperfusion injury ( Wang et al, 2014a ) and lung cancer ( Sayin et al, 2014 ). However, in clinical work, it is usually used as a mucolytic agent ( Li et al, 2018a ) and prototypical antidote administered after an acetaminophen overdose, and little attention has been paid to its antioxidant pharmacological property ( Rushworth and Megson, 2014 ). Recently, several limited clinical trials indicated that NAC may be effective in attenuating hepatic dysfunction and ameliorating NAFLD ( Khoshbaten et al, 2010 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

N-Acetyl Cysteine Ameliorates High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease and Intracellular Triglyceride Accumulation by Preserving Mitochondrial Function

et al. 2021

View full text Add to dashboard Cite

Rationale: Nonalcoholic fatty liver disease (NAFLD) is a kind of metabolic disease characterized by liver steatosis. Excessive reactive oxygen species (ROS) originating from dysfunctional mitochondria is the major pathophysiological contributor in the development of NAFLD and is thought to be a promising therapeutic target. A few reports demonstrate the antioxidative treatments for NAFLD.Methods: Male C57 mice were fed on a normal chow diet (ND) or high-fat diet (HFD) for 8 weeks. PBS or N-acetyl cysteine (NAC) was gavaged to mice. LO2 human liver cell line treated with palmitic acid (PA) was applied as a cellular model. Western blot, immunofluorescence, biochemistry assay, and pathological staining were used to investigate the mechanism of suppressing lipid accumulation of NAC.Results: NAC treatment was able to prevent HFD-induced NAFLD, as evidenced by less hepatic triglyceride accumulation and lipid droplet formation compared with that of mice in the HFD group. NAC could preserve mitochondrial function by inhibiting excessive mitophagy and promoting mitochondria biogenesis to prevent ROS production. NAC also activated Sirt1 and preserved its protein level and subsequently promoted mitochondria biogenesis via deacetylating PGC1a.Conclusion: We demonstrated that NAC may be an effective drug to treat NAFLD, which was related to its antioxidative and mitochondrial protective effect.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

N-Acetyl Cysteine Ameliorates High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease and Intracellular Triglyceride Accumulation by Preserving Mitochondrial Function

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Punctuate epithelial staining was recorded according to the standard National Eye Institute grading system of 0–3 to each of five areas of the cornea: central, superior, inferior, nasal, and temporal (total, 15 points). 12 …”

Section: Methodsmentioning

confidence: 99%

Isotretinoin Impairs the Secretory Function of Meibomian Gland Via the PPARγ Signaling Pathway

Zhang

Tian

Bao

et al. 2022

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

Purpose To investigate the effects of isotretinoin on the ocular surface and to explore the possible mechanisms. Methods Rats were treated with isotretinoin 20 mg/kg/d for five months and tested monthly for tear secretion, fluorescein staining, and infrared photography. After five months of treatment, tissues were harvested for routine staining to evaluate the morphological changes; and real-time polymerase chain reaction, Western blot, and immunohistochemistry to study the expression of associated genes and their products such as forkhead box protein O1 ( FoxO1 ), forkhead box protein O3, peroxisome proliferator–activated receptor γ ( PPARγ ), adipose differentiation–related protein, elongation of very long chain fatty acids protein 4, fatty acid binding protein 4, matrix metalloproteinase-9, and interleukin-6. Results Systemically, isotretinoin-treated rats have a significantly lower body weight that controls and apparent skin damage. Locally, although there was no alteration in tear secretion, a significant corneal involvement indicated by increased fluorescein staining scores, and also the contrast of meibomian gland was significantly reduced but no significant atrophy of the acinus was found. In addition, isotretinoin causes a decrease in conjunctival goblet cells. Furthermore, isotretinoin treatment did not cause the upregulation of FoxO1 and inflammation related genes but significantly suppressed the expression of PPARγ pathway. Conclusions Isotretinoin does not cause a significant atrophy of the acinus and a significant change of FoxO1 expression in the meibomian gland. Isotretinoin causes meibomian gland dysfunction, affecting meibocyte differentiation and qualitative and quantitative changes in the meibum, through PPARγ pathway.

show abstract

“…Furthermore, recently animal models for MAM deficiency were designed by topical application of 10% NAC in male Sprague-Dawley rats for 5 days, four times a day [53]. NAC treated rats showed significant (p < 0.01 compared to controls) decrease in tear secretion, corneal wettability, BUT of TF, tear MUC5AC concentration, and numbers of conjunctival goblet cell.…”

Section: Mam and Corneal Wettabilitymentioning

confidence: 99%

Contribution of Mucins towards the Physical Properties of the Tear Film: A Modern Update

Georgiev

Eftimov

Yokoi

2019

IJMS

View full text Add to dashboard Cite

Instability of the tear film (TF) protecting the ocular surface results in dry eye syndrome (DES), the most prevalent public health ophthalmic disease affecting the quality of life of 10 to 30% of the human population worldwide. Although the impact of the tear film lipid layer (TFLL) and of the aqueous tears (AT) to the TF stability is extensively studied, in contrast the contribution of the secretory mucins (SM) and of the membrane-associated mucins (MAM), i.e., one of the most abundant molecular classes in AT and in the corneal epithelium respectively, remains poorly defined. However, it is well known that in DES both types of mucins are quantitatively or qualitatively deficient. Numerous studies since the 1990s until now have proposed direct involvement of SM and MAM in the material properties (viscoelasticity, hydration, and protection of the ocular surface; synergistic cooperation with the rest of the TF layers; etc.) and stability of TF. These theories will be reviewed here in the context of the classical and modern in vitro and in vivo results that allow their reappraisal and in view of the novel mucin secretion enhancing pharmaceuticals, which have opened innovative routes for the therapy of DES.

show abstract

Effects of Topical Mucolytic Agents on the Tears and Ocular Surface: A Plausible Animal Model of Mucin-Deficient Dry Eye

Abstract: Topical administration of 10% NAC induced ocular surface damage and tear film instability by prompting MUC16 disruption and release from the ocular surface. This animal model could be used to study dry eye disease, especially the mucin-deficiency subtype.

Cited by 18 publications

References 51 publications

N-Acetyl Cysteine Ameliorates High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease and Intracellular Triglyceride Accumulation by Preserving Mitochondrial Function

N-Acetyl Cysteine Ameliorates High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease and Intracellular Triglyceride Accumulation by Preserving Mitochondrial Function

Isotretinoin Impairs the Secretory Function of Meibomian Gland Via the PPARγ Signaling Pathway

Contribution of Mucins towards the Physical Properties of the Tear Film: A Modern Update

Contact Info

Product

Resources

About