Alkali Burn Injury Model of Meibomian Gland Dysfunction in Mice

Overview

Journal Int J Ophthalmol

Specialty Ophthalmology

Date 2024 Dec 19

PMID 39697880

Authors

Yong Li

Ya-Qiong Yang

Yong Lin

Ke Yan

Yu-Fei Lyu

Zhao-Qiang Zhang

Cai-Hong Huang

Jiao-Yue Hu

Zu-Guo Liu

Affiliations

Soon will be listed here.

Abstract

Aim: To establish a stable, short-time, low-cost and reliable murine model of meibomian gland dysfunction (MGD).

Methods: A filter paper sheet soaked in 1.0 mol/L sodium hydroxide (NaOH) solution was used to touch the eyelid margin of C57BL/6J mice for 10s to establish the model. The other eye was left untreated as a control group. Eyelid margin morphological changes and the meibomian glands (MGs) were observed by slit lamp microscopy on days 5 and 10 post-burn. Hematoxylin-eosin (HE) staining and Oil red O staining were adopted in detecting the changes in MGs morphology and lipid deposition. Real-time polymerase chain reaction, Western blot, immunofluorescence staining and immunohistochemical staining were used to detect interleukin (IL)-6, IL-1β, IL-18, tumor necroses factor (TNF)-α, interferon (IFN)-γ, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4), 3-nitroturosine (3-NT), 4-hydroxynonenal (4-HNE) and cytokeratin 10 (K10) expression changes in MGs.

Results: MGs showed plugging of orifice, glandular deficiency, abnormal acinar morphology, ductal dilatation, and lipid deposition after alkali burn. The expressions of IL-6, IL-18, IL-1β, IFN-γ, and TNF-α indicators of inflammation and oxidative stress in MGs tissues were significantly increased. Abnormal keratinization increased in the MG duct.

Conclusion: A murine model of MGD is established by alkali burn of the eyelid margin that matches the clinical presentation of MGD providing a stable, short-time, low-cost, and reliable MGD model. The new method suggests efficient avenues for future research.

References

Miyake H, Oda T, Katsuta O, Seno M, Nakamura M . A Novel Model of Meibomian Gland Dysfunction Induced with Complete Freund's Adjuvant in Rabbits. Vision (Basel). 2019; 1(1). PMC: 6835782. DOI: 10.3390/vision1010010. View

Perez V, Mousa H, Soifer M, Beatty C, Sarantopoulos S, Saban D . Meibomian Gland Dysfunction: A Route of Ocular Graft-Versus-Host Disease Progression That Drives a Vicious Cycle of Ocular Surface Inflammatory Damage. Am J Ophthalmol. 2022; 247:42-60. PMC: 10270654. DOI: 10.1016/j.ajo.2022.09.009. View

Clare G, Bunce C, Tuft S . Amniotic membrane transplantation for acute ocular burns. Cochrane Database Syst Rev. 2022; 9:CD009379. PMC: 9435439. DOI: 10.1002/14651858.CD009379.pub3. View

Cui C, Smith J, Schlessinger D, Chan C . X-linked anhidrotic ectodermal dysplasia disruption yields a mouse model for ocular surface disease and resultant blindness. Am J Pathol. 2005; 167(1):89-95. PMC: 1603450. DOI: 10.1016/S0002-9440(10)62956-2. View

Yu J, Shen Y, Luo J, Jin J, Li P, Feng P . Upadacitinib inhibits corneal inflammation and neovascularization by suppressing M1 macrophage infiltration in the corneal alkali burn model. Int Immunopharmacol. 2023; 116:109680. DOI: 10.1016/j.intimp.2023.109680. View

Meng J, Lin B, Huang S, Li Y, Wu P, Zhang F . Melatonin exerts anti-angiogenic and anti-inflammatory effects in alkali-burned corneas. Ann Transl Med. 2022; 10(8):432. PMC: 9096387. DOI: 10.21037/atm-21-4927. View

Li Q, Hua X, Li L, Zhou X, Tian Y, Deng Y . AIP1 suppresses neovascularization by inhibiting the NOX4-induced NLRP3/NLRP6 imbalance in a murine corneal alkali burn model. Cell Commun Signal. 2022; 20(1):59. PMC: 9074213. DOI: 10.1186/s12964-022-00877-5. View

Ibrahim O, Dogru M, Matsumoto Y, Igarashi A, Kojima T, Wakamatsu T . Oxidative stress induced age dependent meibomian gland dysfunction in Cu, Zn-superoxide dismutase-1 (Sod1) knockout mice. PLoS One. 2014; 9(7):e99328. PMC: 4103776. DOI: 10.1371/journal.pone.0099328. View

Dong Z, Ying M, Zheng J, Hu L, Xie J, Ma Y . Evaluation of a rat meibomian gland dysfunction model induced by closure of meibomian gland orifices. Int J Ophthalmol. 2018; 11(7):1077-1083. PMC: 6048323. DOI: 10.18240/ijo.2018.07.01. View

10.

Watanabe K, Yoshida M, Okumura T, Sassa T, Kihara A, Uchiyama A . Improvement of Evaporative Dry Eye With Meibomian Gland Dysfunction in Model Mice by Treatment With Ophthalmic Solution Containing Mineral Oil. Transl Vis Sci Technol. 2021; 10(4):21. PMC: 8083063. DOI: 10.1167/tvst.10.4.21. View

11.

Shi L, Li L, Sun X, Chen Y, Luo D, He L . Er-Dong-Xiao-Ke decoction regulates lipid metabolism via PPARG-mediated UCP2/AMPK signaling to alleviate diabetic meibomian gland dysfunction. J Ethnopharmacol. 2024; 333:118484. DOI: 10.1016/j.jep.2024.118484. View

12.

Schaumberg D, Nichols J, Papas E, Tong L, Uchino M, Nichols K . The international workshop on meibomian gland dysfunction: report of the subcommittee on the epidemiology of, and associated risk factors for, MGD. Invest Ophthalmol Vis Sci. 2011; 52(4):1994-2005. PMC: 3072161. DOI: 10.1167/iovs.10-6997e. View

13.

Kojima T, Dogru M, Kawashima M, Nakamura S, Tsubota K . Advances in the diagnosis and treatment of dry eye. Prog Retin Eye Res. 2020; :100842. DOI: 10.1016/j.preteyeres.2020.100842. View

14.

Tian L, Guo Y, Wang S, Li Z, Wang N, Jie Y . Efficacy of far infrared functional glasses in the treatment of meibomian gland dysfunction-related dry eye. MedComm (2020). 2024; 5(4):e507. PMC: 10959456. DOI: 10.1002/mco2.507. View

15.

Green-Church K, Butovich I, Willcox M, Borchman D, Paulsen F, Barabino S . The international workshop on meibomian gland dysfunction: report of the subcommittee on tear film lipids and lipid-protein interactions in health and disease. Invest Ophthalmol Vis Sci. 2011; 52(4):1979-93. PMC: 3072160. DOI: 10.1167/iovs.10-6997d. View

16.

Seen S, Tong L . Dry eye disease and oxidative stress. Acta Ophthalmol. 2017; 96(4):e412-e420. DOI: 10.1111/aos.13526. View

17.

Swarup A, Ta C, Wu A . Molecular mechanisms and treatments for ocular symblephara. Surv Ophthalmol. 2021; 67(1):19-30. PMC: 8553799. DOI: 10.1016/j.survophthal.2021.04.008. View

18.

Bu J, Wu Y, Cai X, Jiang N, Jeyalatha M, Yu J . Hyperlipidemia induces meibomian gland dysfunction. Ocul Surf. 2019; 17(4):777-786. DOI: 10.1016/j.jtos.2019.06.002. View

19.

Jester J, Rife L, Nii D, Luttrull J, Wilson L, Smith R . In vivo biomicroscopy and photography of meibomian glands in a rabbit model of meibomian gland dysfunction. Invest Ophthalmol Vis Sci. 1982; 22(5):660-7. View

20.

Jester J, Brown D . Wakayama Symposium: Peroxisome proliferator-activated receptor-gamma (PPARγ) and meibomian gland dysfunction. Ocul Surf. 2012; 10(4):224-9. PMC: 3479436. DOI: 10.1016/j.jtos.2012.07.001. View