A Ligation of the Lacrimal Excretory Duct in Mouse Induces Lacrimal Gland Inflammation with Proliferative Cells

The lacrimal gland secretes tear fluids to ocular surface, which plays an indispensable role in maintaining the health of the ocular epithelia and protecting the ocular surface from the external environment. The dysfunction of the lacrimal glands causes dry eye disease due to a reduction in tear volume. The dry eye disease is becoming a popular public disease, for the number of patients is increasing, who have subjective symptom and loss of vision, which affect the quality of life. Inflammatory change in the damaged lacrimal gland has been reported; however, a major challenge is to establish a simple animal model to observe the changes. Here, we demonstrated an injury model by ligating the main excretory duct of the lacrimal gland, which is a simple and stable way to clearly understand the mechanism of lacrimal gland inflammation. We observed the process of injury and proliferation of the lacrimal gland and detected a population of lacrimal gland epithelial cells with proliferation potential which were also nestin-positive cells following duct ligation. This study successfully established an injury model to observe the tissue injury process of the lacrimal gland, and this model will be useful for analysis of the inflammation and proliferation mechanism in the future.

[1]  M. Ko,et al.  Identification of transcription factors that promote the differentiation of human pluripotent stem cells into lacrimal gland epithelium-like cells , 2017, npj Aging and Mechanisms of Disease.

[2]  K. Tsubota,et al.  Cytokeratin expression in mouse lacrimal gland germ epithelium. , 2016, Experimental eye research.

[3]  K. Tsubota,et al.  Challenges and Strategies for Regenerating the Lacrimal Gland. , 2016, The ocular surface.

[4]  R. Hoffman,et al.  Isoproterenol directs hair follicle-associated pluripotent (HAP) stem cells to differentiate in vitro to cardiac muscle cells which can be induced to form beating heart-muscle tissue sheets , 2016, Cell cycle.

[5]  K. Tsubota,et al.  Tissue Renin–Angiotensin System in Lacrimal Gland Fibrosis in a Murine Model of Chronic Graft-Versus-Host Disease , 2015, Cornea.

[6]  Masatoshi Hirayama [Proof of a Concept for Bioengineered Organ Replacement to Restore Lacrimal Gland Function]. , 2015, Nippon Ganka Gakkai zasshi.

[7]  K. Tsubota,et al.  Bioengineered Lacrimal Gland Organ Regeneration in Vivo , 2015, Journal of functional biomaterials.

[8]  Sabine Weiskirchen,et al.  Bile Duct Ligation in Mice: Induction of Inflammatory Liver Injury and Fibrosis by Obstructive Cholestasis , 2015, Journal of visualized experiments : JoVE.

[9]  M. Oshima,et al.  Development and Prospects of Organ Replacement Regenerative Therapy , 2013, Cornea.

[10]  C. Kruse,et al.  Multipotent Nestin-Positive Stem Cells Reside in the Stroma of Human Eccrine and Apocrine Sweat Glands and Can Be Propagated Robustly In Vitro , 2013, PloS one.

[11]  K. Tsubota,et al.  Functional lacrimal gland regeneration by transplantation of a bioengineered organ germ , 2013, Nature Communications.

[12]  C. Kruse,et al.  Mammary gland-derived nestin-positive cell populations can be isolated from human male and female donors , 2013, Stem Cell Research & Therapy.

[13]  C. Kruse,et al.  Mammary gland-derived nestin-positive cell populations can be isolated from human male and female donors , 2013, Stem Cell Research & Therapy.

[14]  K. Tsubota,et al.  Age-related dysfunction of the lacrimal gland and oxidative stress: evidence from the Cu,Zn-superoxide dismutase-1 (Sod1) knockout mice. , 2012, The American journal of pathology.

[15]  J. Carlson,et al.  Intratarsal keratinous cysts of the meibomian gland (a sebaceous duct cyst): report of 2 cases. , 2011, The American Journal of dermatopathology.

[16]  K. Tsubota,et al.  Comparison of telomere length and association with progenitor cell markers in lacrimal gland between Sjögren syndrome and non-Sjögren syndrome dry eye patients , 2011, Molecular vision.

[17]  K. Tsubota,et al.  Prevalence and risk factors of dry eye disease in Japan: Koumi study. , 2011, Ophthalmology.

[18]  C. Kublin,et al.  Isolation and propagation of mesenchymal stem cells from the lacrimal gland. , 2011, Investigative ophthalmology & visual science.

[19]  S. Amano,et al.  Meibomian Gland Duct Distortion in Patients With Perennial Allergic Conjunctivitis , 2010, Cornea.

[20]  J. Sheen,et al.  Bile duct ligation in developing rats: temporal progression of liver, kidney, and brain damage. , 2010, Journal of pediatric surgery.

[21]  J. Schechter,et al.  A lacrimal gland is a lacrimal gland, but rodent's and rabbit's are not human. , 2010, The ocular surface.

[22]  D. Zoukhri Mechanisms involved in injury and repair of the murine lacrimal gland: role of programmed cell death and mesenchymal stem cells. , 2010, The ocular surface.

[23]  B. Wollenberg,et al.  Glandular tissue from human pancreas and salivary gland yields similar stem cell populations. , 2009, European journal of cell biology.

[24]  K. Tsubota,et al.  Japan Ministry of Health study on prevalence of dry eye disease among Japanese high school students. , 2008, American journal of ophthalmology.

[25]  J. Alroy,et al.  Mechanisms of murine lacrimal gland repair after experimentally induced inflammation. , 2008, Investigative ophthalmology & visual science.

[26]  C. Kublin,et al.  A single injection of interleukin-1 induces reversible aqueous-tear deficiency, lacrimal gland inflammation, and acinar and ductal cell proliferation. , 2007, Experimental eye research.

[27]  Robert M Hoffman,et al.  Implanted hair follicle stem cells form Schwann cells that support repair of severed peripheral nerves. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[28]  Anthony Atala,et al.  Tissue engineering, stem cells and cloning: current concepts and changing trends , 2005, Expert opinion on biological therapy.

[29]  Robert M Hoffman,et al.  Multipotent nestin-positive, keratin-negative hair-follicle bulge stem cells can form neurons. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[30]  Meng Yang,et al.  Nestin expression in hair follicle sheath progenitor cells , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[31]  Tetsurou Yamamoto,et al.  Salivary gland progenitor cells induced by duct ligation differentiate into hepatic and pancreatic lineages , 2003, Hepatology.

[32]  Yukihiro Matsumoto,et al.  Improved functional visual acuity after punctal occlusion in dry eye patients. , 2003, American journal of ophthalmology.

[33]  K. Tsubota,et al.  Treatment of severe dry eye , 1996, The Lancet.

[34]  F. Jakobiec,et al.  Extensive squamous hyperplasia of the meibomian duct in acne rosacea. , 1994, Archives of ophthalmology.

[35]  J. R. Garrett,et al.  Secretory activity and the myoepithelial cells of salivary glands after duct ligation in cats. , 1974, Archives of oral biology.

[36]  S. Mishima,et al.  SOME PHYSIOLOGICAL ASPECTS OF THE PRECORNEAL TEAR FILM. , 1965, Archives of ophthalmology.

[37]  R. Hoffman Multipotent Stem Cells of the Hair Follicle , 2016, Methods in Molecular Biology.

[38]  R. Meech,et al.  Lacrimal Gland Repair Using Progenitor Cells. , 2016, Stem cells translational medicine.

[39]  É. Mezey,et al.  Bone marrow-derived cells rescue salivary gland function in mice with head and neck irradiation. , 2011, The international journal of biochemistry & cell biology.

[40]  J. Hureau,et al.  The arteries of the lacrimal gland , 2005, Anatomia Clinica.

[41]  V. Brightman,et al.  The effects of desalivation by duct ligation or salivary gland extirpation on taste preference in rats. , 1981, Archives of oral biology.