Sex differences in lacrimal gland lesions in a streptozotocin-induced diabetic mouse model

Tingting Xu ( Clinical Medical College, Shandong Second Medical University, Weifang, Shangdong, 261021, China )

Lingling Yang ( Corneal Disease Department, Shandong Ophthalmology Institute, Qingdao, Shandong, 266000, China )

Jun Cheng ( Ophthalmology Laboratory, Shandong Ophthalmology Institute, Qingdao, Shandong, 266000, China )

https://doi.org/10.37155/3060-8708-0206-1

Abstract

Objective: To investigate gender-based differences in the progression of lacrimal gland lesions in diabetic mice. Methods: Sixty-four C57BL/6 mice of each sex (64 males, 64 females) were used. Mice of each sex were divided into a diabetic group and a control group (n = 32 per group). The diabetic group received intraperitoneal streptozotocin for five consecutive days; controls received citrate buffer. At 1, 2, 3, and 8 months post-injection, body weight, blood glucose, corneal sensitivity, and tear secretion were measured. Lacrimal glands were examined histologically and for inflammatory factor expression. Results: Diabetic mice showed significantly lower body weight and tear secretion, and higher blood glucose than controls at all time points. Male diabetic mice exhibited greater body weight loss than females throughout, and greater tear reduction at 1 month. Corneal sensitivity decreased significantly in diabetics from 2 months onward, with no sex difference. Lacrimal gland weight was significantly reduced in diabetics at 3 and 8 months, with greater reduction in males. Inflammatory cell infiltration appeared at 3 months and intensified by 8 months in both sexes. At 8 months, TNF-α and IL-1β expression was significantly elevated in diabetic males but not females. Conclusion: Both male and female diabetic mice developed dry eye-related pathologies, but males showed more severe lacrimal gland lesions, suggesting they may be a more suitable model for studying diabetic lacrimal gland complications.

Keywords

Diabetes; Mouse model; Lacrimal Gland Lesions; Sex Differences; Dry Eye-related Pathologies

Full Text

PDF

References

[1] Abel ED, Gloyn AL, Evans-Molina C, et al. Diabetes mellitus-Progress and opportunities in the evolving epidemic. Cell, 2024;187(15):3789-3820. https://doi.org/10.1016/j.cell.2024.06.029.
[2] Li Y, Teng D, Shi X, et al. Prevalence of diabetes recorded in mainland China using 2018 diagnostic criteria from the American Diabetes Association: national cross sectional study. BMJ, 2020;369:m997. https://doi.org/10.1136/bmj.m997.
[3] Ghenciu DM, Dănilă AI, Stoicescu ER, et al. Tear Film Alterations in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis. Diagnostics (Basel), 2025;15(24):3104. https://doi.org/10.3390/diagnostics15243104.
[4] Hao Y, Wu B, Feng J, et al. Relationship between type 2 diabetes mellitus and changes of the lid margin, meibomian gland and tear film in dry eye patients: a cross-sectional study. International ophthalmology, 2025;45(1):261. https://doi.org/10.1007/s10792-025-03636-w.
[5] Ghenciu LA, Hațegan OA, Bolintineanu SL, et al. Immune-Mediated Ocular Surface Disease in Diabetes Mellitus-Clinical Perspectives and Treatment: A Narrative Review. Biomedicines, 2024;12(6):1303. https://doi.org/10.3390/biomedicines12061303.
[6] Fogagnolo P, Torregrossa G, Tranchina L, et al. Tear Film Osmolarity, Ocular Surface Disease and Glaucoma: A Review. Current medicinal chemistry, 2019;26(22):4241-4252. https://doi.org/10.2174/0929867326666190725160621.
[7] Ohno Y, Satoh K, Kashimata M. Review of genes potentially related to hyposecretion in male non-obese diabetic (NOD) mice, a Sjögren's syndrome model. Journal of oral biosciences, 2023;65(3):211-217. https://doi.org/10.1016/j.job.2023.05.001
[8] Craig JP, Nelson JD, Azar DT, et al. TFOS DEWS II Report Executive Summary. The ocular surface, 2017;15(4):802-812. https://doi.org/10.1016/j.jtos.2017.08.003.
[9] Song X, Zhao P, Wang G, et al. The effects of estrogen and androgen on tear secretion and matrix metalloproteinase-2 expression in lacrimal glands of ovariectomized rats. Investigative ophthalmology & visual science, 2014;55(2):745-751. https://doi.org/10.1167/iovs.12-10457.
[10] Kaštelan S, Hat K, Tomić Z, et al. Sex Differences in the Lacrimal Gland: Implications for Dry Eye Disease. International journal of molecular sciences, 2025;26(8):3833. https://doi.org/10.3390/ijms26083833.
[11] Mu PY, Chu CC, Yu D, et al. PPARγ: the dominant regulator among PPARs in dry eye lacrimal gland and diabetic lacrimal gland. International journal of ophthalmology, 2020;13(6):860-869. https://doi.org/10.18240/ijo.2020.06.02.
[12] Qu M, Wang Q, Bai X, et al. A gatekeeper sympathetic control of lacrimal tear secretion and dry eye onset through the NA-Adra1a-Ucp2 pathway. Nature communications, 2025;16(1):5215. https://doi.org/10.1038/s41467-025-60476-z.
[13] Módulo CM, Jorge AG, Dias AC, et al. Influence of insulin treatment on the lacrimal gland and ocular surface of diabetic rats. Endocrine, 2009;36(1):161-168. https://doi.org/10.1007/s12020-009-9208-9.
[14] Messmer EM. The pathophysiology, diagnosis, and treatment of dry eye disease. Deutsches Arzteblatt international, 2015;112(5):71-82. https://doi.org/10.3238/arztebl.2015.0071.
[15] Peck T, Olsakovsky L, Aggarwal S. Dry Eye Syndrome in Menopause and Perimenopausal Age Group. Journal of mid-life health, 2017;(2):51-54. https://doi.org/10.4103/jmh.JMH_41_17.
[16] Yeung A, Dwarakanathan S. Diabetic keratopathy. Disease-a-month: DM, 2021;67(5):101135. https://doi.org/10.1016/j.disamonth.2021.101135.
[17] Clayton JA. Dry Eye. The New England journal of medicine, 2018;378(23): 2212-2223. https://doi.org/10.1056/NEJMra1407936.

Copyright © 2025 Tingting Xu,Lingling Yang,Jun Cheng Creative Commons License Publishing time:2025-12-31
This work is licensed under a Creative Commons Attribution 4.0 International License