Skip to main content
Erschienen in: International Ophthalmology 2/2023

30.07.2022 | Original Paper

Tear film instability is associated with weakened colocalization between occludin and MUC5AC in scopolamine-induced dry eye disease (DED) rats

verfasst von: Kun Xu, Xian-ning Liu, Hong-bing Zhang, Xiu-ping Zhu, Xian-jiao Zhang

Erschienen in: International Ophthalmology | Ausgabe 2/2023

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Dry eye disease (DED) is a disease with tear film instability because of multiple factors. This study was conducted to explore roles of occludin and MUC5AC in tear film instability in DED rat model.

Methods

A total of 20 SD rats were divided into DED group (n = 10) and normal control (NC) group (n = 10). DED rat model was established by subcutaneously injecting with scopolamine hydrobromide. Clinical examinations, including tear breakup time (tBUT), Schirmer’s test and corneal fluorescein staining, were conducted to determine corneal functions. Transmission electron microscopy was used to measure the ultrastructures of corneal epithelial cells. Western blotting assay was used to identify occludin expression in corneal tissues of DED rats. Real-time PCR (RT-PCR) was performed to verify gene transcription of occludin and MUC5AC. Colocalization between occludin and MUC5AC was identified with confocal fluorescence microscopy.

Results

Tear breakup time was significantly shorter, and corneal fluorescein staining score was predominantly higher in DED rats compared to those in normal rats (P < 0.05). Normal rats showed a steady tear secretion throughout the whole experiments, while DED rats showed a dramatic reduction on day 14. DED rats demonstrated ultrastructural damage of Golgi apparatus and endoplasmic reticulum in corneal epithelial cells. Occludin and MUC5AC expressions were significantly downregulated in corneal tissue of DED rats compared with those of normal rats (P < 0.05). Percentage of occludin-MUC5AC-colocalized corneal epithelial cells in DED rats was significantly less compared with those in normal rats (P < 0.01).

Conclusions

Tear film stability was damaged in scopolamine-induced DED rats because of the weakened colocalization between occludin and MUC5AC molecule. This study would provide a potential clue for the pathogenesis and a promising theoretical basis for clinical work of DED.
Literatur
1.
Zurück zum Zitat Chinese branch of the asian dry eye society, ocular surface and tear film diseases group of ophthalmology committee of cross-straits medicine exchange association, ocular surface and dry eye group of Chinese ophthalmologist association. Expert consensus on dry eye in China: dry eye related to eye surgery (2021) Zhonghua Yan Ke Za Zhi 2021;57:564–572 Chinese branch of the asian dry eye society, ocular surface and tear film diseases group of ophthalmology committee of cross-straits medicine exchange association, ocular surface and dry eye group of Chinese ophthalmologist association. Expert consensus on dry eye in China: dry eye related to eye surgery (2021) Zhonghua Yan Ke Za Zhi 2021;57:564–572
2.
Zurück zum Zitat Craig JP, Nichols KK, Akpek EK et al (2017) TFOS DEWS II definition and classification report. Ocul Surf 15:276–283CrossRefPubMed Craig JP, Nichols KK, Akpek EK et al (2017) TFOS DEWS II definition and classification report. Ocul Surf 15:276–283CrossRefPubMed
3.
Zurück zum Zitat Golden MI, Meyer JJ, Patel BC (2021) Dry eye syndrome. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing, Tampa, 2022 Jan Golden MI, Meyer JJ, Patel BC (2021) Dry eye syndrome. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing, Tampa, 2022 Jan
4.
Zurück zum Zitat Messmer EM (2015) The pathophysiology, diagnosis, and treatment of dry eye disease. Dtsch Arztebl Int 112:71–81PubMedPubMedCentral Messmer EM (2015) The pathophysiology, diagnosis, and treatment of dry eye disease. Dtsch Arztebl Int 112:71–81PubMedPubMedCentral
5.
Zurück zum Zitat Lemp MA, Foulks GN (2007) The definition and classification of dry eye disease: report of the definition and classification subcommittee of the international dry eye workshop (2007). Ocul Surf 5:75–92CrossRef Lemp MA, Foulks GN (2007) The definition and classification of dry eye disease: report of the definition and classification subcommittee of the international dry eye workshop (2007). Ocul Surf 5:75–92CrossRef
6.
Zurück zum Zitat Fini ME, Bauskar A, Jeong S, Wilson MR (2016) Clusterin in the eye: an old dog with new tricks at the ocular surface. Exp Eye Res 147:57–71CrossRefPubMed Fini ME, Bauskar A, Jeong S, Wilson MR (2016) Clusterin in the eye: an old dog with new tricks at the ocular surface. Exp Eye Res 147:57–71CrossRefPubMed
7.
Zurück zum Zitat Wu MF, Gao H, Zhao LJ, Chen H, Huang YK (2020) Real dynamic assessment of tear film optical quality for monitoring and early prevention of dry eye. Medicine (Baltimore) 99:e21494CrossRefPubMed Wu MF, Gao H, Zhao LJ, Chen H, Huang YK (2020) Real dynamic assessment of tear film optical quality for monitoring and early prevention of dry eye. Medicine (Baltimore) 99:e21494CrossRefPubMed
9.
Zurück zum Zitat Shimazaki-Den S, Dogru M, Higa K, Shimazaki J (2013) Symptoms, visual function, and mucin expression of eyes with tear film instability. Cornea 32:1211–1218CrossRefPubMed Shimazaki-Den S, Dogru M, Higa K, Shimazaki J (2013) Symptoms, visual function, and mucin expression of eyes with tear film instability. Cornea 32:1211–1218CrossRefPubMed
10.
Zurück zum Zitat Woodward AM, Senchyna M, Argüeso P (2021) Short-term reproducibility of MUC5AC measurement in human tear fluid. Diagnostics (Basel) 11:57CrossRefPubMed Woodward AM, Senchyna M, Argüeso P (2021) Short-term reproducibility of MUC5AC measurement in human tear fluid. Diagnostics (Basel) 11:57CrossRefPubMed
11.
Zurück zum Zitat Liu W, Li H, Lu D et al (2010) The tear fluid mucin 5AC change of primary angle-closure glaucoma patients after short-term medications and phacotrabeculectomy. Mol Vis 16:2342–2346PubMedPubMedCentral Liu W, Li H, Lu D et al (2010) The tear fluid mucin 5AC change of primary angle-closure glaucoma patients after short-term medications and phacotrabeculectomy. Mol Vis 16:2342–2346PubMedPubMedCentral
13.
Zurück zum Zitat Putra I, Rabiee B, Anwar KN et al (2019) Staphylococcus aureus alpha-hemolysin impairs corneal epithelial wound healing and promotes intracellular bacterial invasion. Exp Eye Res 181:263–270CrossRefPubMedPubMedCentral Putra I, Rabiee B, Anwar KN et al (2019) Staphylococcus aureus alpha-hemolysin impairs corneal epithelial wound healing and promotes intracellular bacterial invasion. Exp Eye Res 181:263–270CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Pu Q, Guo XX, Hu JJ, Li AL, Li GG, Li XY (2022) Nicotinamide mononucleotide increases cell viability and restores tight junctions in high-glucose-treated human corneal epithelial cells via the SIRT1/Nrf2/HO-1 pathway. Biomed Pharmacother 147:112659CrossRefPubMed Pu Q, Guo XX, Hu JJ, Li AL, Li GG, Li XY (2022) Nicotinamide mononucleotide increases cell viability and restores tight junctions in high-glucose-treated human corneal epithelial cells via the SIRT1/Nrf2/HO-1 pathway. Biomed Pharmacother 147:112659CrossRefPubMed
15.
16.
Zurück zum Zitat Jiang Y, Song J, Xu Y et al (2021) Piezo1 regulates intestinal epithelial function by affecting the tight junction protein claudin-1 via the ROCK pathway. Life Sci 275:119254CrossRefPubMed Jiang Y, Song J, Xu Y et al (2021) Piezo1 regulates intestinal epithelial function by affecting the tight junction protein claudin-1 via the ROCK pathway. Life Sci 275:119254CrossRefPubMed
17.
Zurück zum Zitat McDermott JR, Bartram RE, Knight PA, Miller HR, Garrod DR, Grencis RK (2003) Mast cells disrupt epithelial barrier function during enteric nematode infection. Proc Natl Acad Sci USA 100:7761–7766CrossRefPubMedPubMedCentral McDermott JR, Bartram RE, Knight PA, Miller HR, Garrod DR, Grencis RK (2003) Mast cells disrupt epithelial barrier function during enteric nematode infection. Proc Natl Acad Sci USA 100:7761–7766CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Kim KA, Kim D, Kim JH et al (2020) Autophagy-mediated occludin degradation contributes to blood–brain barrier disruption during ischemia in bEnd. 3 brain endothelial cells and rat ischemic stroke models. Fluids Barriers CNS 17:21CrossRefPubMedPubMedCentral Kim KA, Kim D, Kim JH et al (2020) Autophagy-mediated occludin degradation contributes to blood–brain barrier disruption during ischemia in bEnd. 3 brain endothelial cells and rat ischemic stroke models. Fluids Barriers CNS 17:21CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Wang Z, Wade P, Mandell KJ et al (2007) Raf 1 represses expression of the tight junction protein occludin via activation of the zinc-finger transcription factor slug. Oncogene 26:1222–1230CrossRefPubMed Wang Z, Wade P, Mandell KJ et al (2007) Raf 1 represses expression of the tight junction protein occludin via activation of the zinc-finger transcription factor slug. Oncogene 26:1222–1230CrossRefPubMed
20.
Zurück zum Zitat Zhang C, Xie H, Yang Q et al (2019) Erythropoietin protects outer blood-retinal barrier in experimental diabetic retinopathy by up-regulating ZO-1 and occludin. Clin Exp Ophthalmol 47:1182–1197CrossRefPubMed Zhang C, Xie H, Yang Q et al (2019) Erythropoietin protects outer blood-retinal barrier in experimental diabetic retinopathy by up-regulating ZO-1 and occludin. Clin Exp Ophthalmol 47:1182–1197CrossRefPubMed
21.
Zurück zum Zitat Lv Y, Chu C, Liu K et al (2021) A combination of CMC and α-MSH inhibited ROS activated NLRP3 inflammasome in hyperosmolarity stressed HCECs and scopolamine-induced dry eye rats. Sci Rep 11:1184CrossRefPubMedPubMedCentral Lv Y, Chu C, Liu K et al (2021) A combination of CMC and α-MSH inhibited ROS activated NLRP3 inflammasome in hyperosmolarity stressed HCECs and scopolamine-induced dry eye rats. Sci Rep 11:1184CrossRefPubMedPubMedCentral
22.
Zurück zum Zitat Chu YY, Hua N, Ru YS, Zhao SZ (2017) The protection of hydrogen-rich saline on a rat dry eye model induced by scopolamine hydrobromide. Zhonghua Yan Ke Za Zhi 53:363–372PubMed Chu YY, Hua N, Ru YS, Zhao SZ (2017) The protection of hydrogen-rich saline on a rat dry eye model induced by scopolamine hydrobromide. Zhonghua Yan Ke Za Zhi 53:363–372PubMed
23.
Zurück zum Zitat Ru Y, Huang Y, Liu H et al (2015) α-Melanocyte-stimulating hormone ameliorates ocular surface dysfunctions and lesions in a scopolamine-induced dry eye model via PKA-CREB and MEK-Erk pathways. Sci Rep 5:18619CrossRefPubMedPubMedCentral Ru Y, Huang Y, Liu H et al (2015) α-Melanocyte-stimulating hormone ameliorates ocular surface dysfunctions and lesions in a scopolamine-induced dry eye model via PKA-CREB and MEK-Erk pathways. Sci Rep 5:18619CrossRefPubMedPubMedCentral
24.
Zurück zum Zitat Sakamoto R, Bennett ES, Henry VA et al (1993) The phenol red thread tear test: a cross-cultural study. Invest Ophthalmol Vis Sci 34:3510–4354PubMed Sakamoto R, Bennett ES, Henry VA et al (1993) The phenol red thread tear test: a cross-cultural study. Invest Ophthalmol Vis Sci 34:3510–4354PubMed
25.
Zurück zum Zitat Pauly A, Brignole-Baudouin F, Labbé A, Liang H, Warnet JM, Baudouin C (2007) New tools for the evaluation of toxic ocular surface changes in the rat. Invest Ophthalmol Vis Sci 48:5473–5483CrossRefPubMed Pauly A, Brignole-Baudouin F, Labbé A, Liang H, Warnet JM, Baudouin C (2007) New tools for the evaluation of toxic ocular surface changes in the rat. Invest Ophthalmol Vis Sci 48:5473–5483CrossRefPubMed
27.
Zurück zum Zitat Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(–Delta Delta C(T)) Method. Methods 25:402–408CrossRefPubMed Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(–Delta Delta C(T)) Method. Methods 25:402–408CrossRefPubMed
29.
Zurück zum Zitat Choi SY, Eom Y, Kim JY, Jang DH, Song JS, Kim HM (2020) Effect of natural extract eye drops in dry eye disease rats. Int J Ophthalmol 13:1023–1030CrossRefPubMedPubMedCentral Choi SY, Eom Y, Kim JY, Jang DH, Song JS, Kim HM (2020) Effect of natural extract eye drops in dry eye disease rats. Int J Ophthalmol 13:1023–1030CrossRefPubMedPubMedCentral
30.
Zurück zum Zitat Surmacz HU, Cotlinski AL, Gehlen ML, Nisihara R, Skare TL (2021) Dry eye and percentage of body fat: a cross-sectional prospective study. Int Ophthalmol 41:1855–1861CrossRefPubMed Surmacz HU, Cotlinski AL, Gehlen ML, Nisihara R, Skare TL (2021) Dry eye and percentage of body fat: a cross-sectional prospective study. Int Ophthalmol 41:1855–1861CrossRefPubMed
31.
Zurück zum Zitat Drevets WC, Zarate CA, Furey ML (2013) Antidepressant effects of the muscarinic cholinergic receptor antagonist scopolamine: a review. Biol Psychiatry 73:1156–1163CrossRefPubMed Drevets WC, Zarate CA, Furey ML (2013) Antidepressant effects of the muscarinic cholinergic receptor antagonist scopolamine: a review. Biol Psychiatry 73:1156–1163CrossRefPubMed
32.
Zurück zum Zitat Lemp MA (2008) Advances in understanding and managing dry eye disease. Am J Ophthalmol 146:350–356CrossRefPubMed Lemp MA (2008) Advances in understanding and managing dry eye disease. Am J Ophthalmol 146:350–356CrossRefPubMed
33.
Zurück zum Zitat Bandamwar KL, Papas EB, Garrett Q (2014) Fluorescein staining and physiological state of corneal epithelial cells. Cont Lens Anterior Eye 37:213–223CrossRefPubMed Bandamwar KL, Papas EB, Garrett Q (2014) Fluorescein staining and physiological state of corneal epithelial cells. Cont Lens Anterior Eye 37:213–223CrossRefPubMed
34.
Zurück zum Zitat Ramkumar HL, Zhang J, Chan CC (2010) Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD). Prog Retin Eye Res 29:169–190CrossRefPubMedPubMedCentral Ramkumar HL, Zhang J, Chan CC (2010) Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD). Prog Retin Eye Res 29:169–190CrossRefPubMedPubMedCentral
35.
Zurück zum Zitat Ru YX, Zhao SX, Dong SX, Liang HY, Wang Y (2018) Systematic alteration of apoptosis: a review with ultrastructural observations on leukemia cells in vivo. Ultrastruct Pathol 42:1–9CrossRefPubMed Ru YX, Zhao SX, Dong SX, Liang HY, Wang Y (2018) Systematic alteration of apoptosis: a review with ultrastructural observations on leukemia cells in vivo. Ultrastruct Pathol 42:1–9CrossRefPubMed
36.
37.
Zurück zum Zitat Hampel U, Garreis F, Burgemeister F, Eßel N, Paulsen F (2018) Effect of intermittent shear stress on corneal epithelial cells using an in vitro flow culture model. Ocul Surf 16:341–351CrossRefPubMed Hampel U, Garreis F, Burgemeister F, Eßel N, Paulsen F (2018) Effect of intermittent shear stress on corneal epithelial cells using an in vitro flow culture model. Ocul Surf 16:341–351CrossRefPubMed
38.
Zurück zum Zitat Liu JJ, Zhang T, Mi YM (2019) Effects of respiratory syncytial virus infection on epidermal growth factor receptor, tight junction association proteins and mucin in airway epithelial cells. Zhongguo Dang Dai Er Ke Za Zhi 21:294–299PubMed Liu JJ, Zhang T, Mi YM (2019) Effects of respiratory syncytial virus infection on epidermal growth factor receptor, tight junction association proteins and mucin in airway epithelial cells. Zhongguo Dang Dai Er Ke Za Zhi 21:294–299PubMed
Metadaten
Titel
Tear film instability is associated with weakened colocalization between occludin and MUC5AC in scopolamine-induced dry eye disease (DED) rats
verfasst von
Kun Xu
Xian-ning Liu
Hong-bing Zhang
Xiu-ping Zhu
Xian-jiao Zhang
Publikationsdatum
30.07.2022
Verlag
Springer Netherlands
Erschienen in
International Ophthalmology / Ausgabe 2/2023
Print ISSN: 0165-5701
Elektronische ISSN: 1573-2630
DOI
https://doi.org/10.1007/s10792-022-02443-x

Weitere Artikel der Ausgabe 2/2023

International Ophthalmology 2/2023 Zur Ausgabe

Neu im Fachgebiet Augenheilkunde

Metastase in der periokulären Region

Metastasen Leitthema

Orbitale und periokuläre metastatische Tumoren galten früher als sehr selten. Aber mit der ständigen Aktualisierung von Medikamenten und Nachweismethoden für die Krebsbehandlung werden neue Chemotherapien und Strahlenbehandlungen eingesetzt. Die …

Staging und Systemtherapie bei okulären und periokulären Metastasen

Metastasen Leitthema

Metastasen bösartiger Erkrankungen sind die häufigsten Tumoren, die im Auge diagnostiziert werden. Sie treten bei ungefähr 5–10 % der Patienten mit soliden Tumoren im Verlauf der Erkrankung auf. Besonders häufig sind diese beim Mammakarzinom und …

Wundheilung nach Trabekulektomie

Trabekulektomie CME-Artikel

Die überschießende Wundheilung in der filtrierenden Glaukomchirurgie ist ein zentraler Faktor für ein operatives Versagen. Nach der Einführung der Trabekulektomie in den 1960er-Jahren wurden viele Faktoren erkannt, die mit einer vermehrten …

„standard operating procedures“ (SOP) – Vorschlag zum therapeutischen Management bei periokulären sowie intraokulären Metastasen

Metastasen Leitthema

Peri- sowie intraokuläre Metastasen sind insgesamt gesehen selten und meist Zeichen einer fortgeschrittenen primären Tumorerkrankung. Die Therapie ist daher zumeist palliativ und selten kurativ. Zudem ist die Therapiefindung sehr individuell. Die …

Update Augenheilkunde

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.