Lacrimal Gland–Ocular Surface Interaction in Sjögrenʼs Syndrome

Dry eye syndrome (DES) is a corneal disease often characterized by an irritating, itching feeling in the eyes and light sensitivity. Inflammation and endoplasmic reticulum (ER) stress may play a crucial role in the pathogenesis of DES, although the underlying mechanism remains elusive. Aster koraiensis has been used traditionally as an edible herb in Korea. It has been reported to have wound-healing and inhibitory effects against insulin resistance and inflammation. Here, we examined the inhibitory effects of inflammation and ER stress by A. koraiensis extract (AKE) in animal model and human retinal pigmented epithelial (ARPE-19) cells. Oral administration of AKE mitigated DE symptoms, including reduced corneal epithelial thickness, increased the gap between lacrimal gland tissues in experimental animals and decreased tear production. It also inhibited inflammatory responses in the corneal epithelium and lacrimal gland. Consequently, the activation of NF-κB was attenuated by the suppression of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Moreover, AKE treatment ameliorated TNF-α-inducible ocular inflammation and thapsigargin (Tg)-inducible ER stress in animal model and human retinal pigmented epithelial (ARPE-19) cells. These results prove that AKE prevents detrimental functional and histological remodeling on the ocular surface and in the lacrimal gland through inhibition of inflammation and ER stress, suggesting its potential as functional food material for improvement of DES.

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THE LACRIMAL GLAND, CONJUNCTIVA AND LACRIMAL DRAINAGE SYSTEM MAY FORM A FUNCTIONAL UNIT FOR OCULAR SURFACE DEFENSE.

Cornea ◽

10.1097/00003226-200011002-00098 ◽

2000 ◽

Vol 19 (Supplement 2) ◽

pp. S100

Author(s):

Erich Knop ◽

Nadja Knop

Keyword(s):

Lacrimal Gland ◽

Ocular Surface ◽

Functional Unit ◽

Drainage System ◽

Lacrimal Drainage System ◽

Lacrimal Drainage

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Immunology of the lacrimal gland, tear film and ocular surface

Graefe s Archive for Clinical and Experimental Ophthalmology ◽

10.1007/s00417-006-0366-7 ◽

2006 ◽

Vol 245 (3) ◽

pp. 471-471

Author(s):

K. Matti Saari

Keyword(s):

Lacrimal Gland ◽

Ocular Surface ◽

Tear Film

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Review: The Lacrimal Gland and Its Role in Dry Eye

Journal of Ophthalmology ◽

10.1155/2016/7542929 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 37

Author(s):

Christopher D. Conrady ◽

Zachary P. Joos ◽

Bhupendra C. K. Patel

Keyword(s):

Dry Eye ◽

Lacrimal Gland ◽

Ocular Surface ◽

Tear Film ◽

Burning Pain ◽

Layered Coating ◽

Accessory Glands ◽

Multiple Components ◽

Blurry Vision

The human tear film is a 3-layered coating of the surface of the eye and a loss, or reduction, in any layer of this film may result in a syndrome of blurry vision and burning pain of the eyes known as dry eye. The lacrimal gland and accessory glands provide multiple components to the tear film, most notably the aqueous. Dysfunction of these glands results in the loss of aqueous and other products required in ocular surface maintenance and health resulting in dry eye and the potential for significant surface pathology. In this paper, we have reviewed products of the lacrimal gland, diseases known to affect the gland, and historical and emerging dry eye therapies targeting lacrimal gland dysfunction.

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Effects of Topical Gabapentin on Ocular Pain and Tear Secretion

Frontiers in Pharmacology ◽

10.3389/fphar.2021.671238 ◽

2021 ◽

Vol 12 ◽

Author(s):

Maurizio Cammalleri ◽

Rosario Amato ◽

Melania Olivieri ◽

Salvatore Pezzino ◽

Paola Bagnoli ◽

...

Keyword(s):

Lacrimal Gland ◽

Ocular Surface ◽

Rabbit Model ◽

Corneal Epithelial Cell ◽

Epithelial Cell Line ◽

Eye Drops ◽

Aquaporin 5 ◽

Ocular Pain ◽

Anesthetic Drugs ◽

Anti Inflammatory

Neuropathic ocular pain is a frequent occurrence in medium to severe dry eye disease (DED). Only palliative treatments, such as lubricants and anti-inflammatory drugs, are available to alleviate patients’ discomfort. Anesthetic drugs are not indicated, because they may interfere with the neural feedback between the cornea and the lacrimal gland, impairing tear production and lacrimation. Gabapentin (GBT) is a structural analog of gamma-amino butyric acid that has been used by systemic administration to provide pain relief in glaucomatous patients. We have already shown in a rabbit model system that its topic administration as eye drops has anti-inflammatory properties. We now present data on rabbits’ eyes showing that indeed GBT given topically as eye drops has analgesic but not anesthetic effects. Therefore, opposite to an anesthetic drug such as oxybuprocaine, GBT does not decrease lacrimation, but–unexpectedly–even stimulates it, apparently through the upregulation of acetylcholine and norepinephrine, and by induction of aquaporin 5 (AQP5) expression in the lacrimal gland. Moreover, data obtained in vitro on a primary human corneal epithelial cell line also show direct induction of AQP5 by GBT. This suggests that corneal cells might also contribute to the lacrimal stimulation promoted by GBT and participate with lacrimal glands in the restoration of the tear film, thus reducing friction on the ocular surface, which is a known trigger of ocular pain. In conclusion, GBT is endowed with analgesic, anti-inflammatory and secretagogue properties, all useful to treat neuropathic pain of the ocular surface, especially in case of DED.

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

Stem Cells International ◽

10.1155/2017/4923426 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 5

Author(s):

Ying Liu ◽

Masatoshi Hirayama ◽

Tetsuya Kawakita ◽

Kazuo Tsubota

Keyword(s):

Dry Eye ◽

Lacrimal Gland ◽

Ocular Surface ◽

Tissue Injury ◽

Dry Eye Disease ◽

Excretory Duct ◽

Eye Disease ◽

Injury Model ◽

Duct Ligation ◽

Number Of Patients

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.

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Lacrimal Gland, Ocular Surface, and Dry Eye

Journal of Ophthalmology ◽

10.1155/2016/7397694 ◽

2016 ◽

Vol 2016 ◽

pp. 1-2 ◽

Cited By ~ 2

Author(s):

Chuanqing Ding ◽

Edit Tóth-Molnár ◽

Ningli Wang ◽

Lei Zhou

Keyword(s):

Dry Eye ◽

Lacrimal Gland ◽

Ocular Surface

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Rapamycin Eyedrops Increased CD4+Foxp3+ Cells and Prevented Goblet Cell Loss in the Aged Ocular Surface

International Journal of Molecular Sciences ◽

10.3390/ijms21238890 ◽

2020 ◽

Vol 21 (23) ◽

pp. 8890

Author(s):

Claudia M. Trujillo-Vargas ◽

Shallu Kutlehria ◽

Humberto Hernandez ◽

Rodrigo G. de Souza ◽

Andrea Lee ◽

...

Keyword(s):

Goblet Cell ◽

Lacrimal Gland ◽

Ocular Surface ◽

Vascular Endothelial Cell ◽

Cell Loss ◽

The Elderly ◽

Inflammatory Disorder ◽

Pronounced Increase ◽

Chronic Inflammatory Disorder ◽

Ifn Γ

Dry eye disease (DED), one of the most prevalent conditions among the elderly, is a chronic inflammatory disorder that disrupts tear film stability and causes ocular surface damage. Aged C57BL/6J mice spontaneously develop DED. Rapamycin is a potent immunosuppressant that prolongs the lifespan of several species. Here, we compared the effects of daily instillation of eyedrops containing rapamycin or empty micelles for three months on the aged mice. Tear cytokine/chemokine profile showed a pronounced increase in vascular endothelial cell growth factor-A (VEGF-A) and a trend towards decreased concentration of Interferon gamma (IFN)-γ in rapamycin-treated groups. A significant decrease in inflammatory markers in the lacrimal gland was also evident (IFN-γ, IL-12, CIITA and Ctss); this was accompanied by slightly diminished Unc-51 Like Autophagy Activating Kinase 1 (ULK1) transcripts. In the lacrimal gland and draining lymph nodes, we also observed a significant increase in the CD45+CD4+Foxp3+ cells in the rapamycin-treated mice. More importantly, rapamycin eyedrops increased conjunctival goblet cell density and area compared to the empty micelles. Taken together, evidence from these studies indicates that topical rapamycin has therapeutic efficacy for age-associated ocular surface inflammation and goblet cell loss and opens the venue for new investigations on its role in the aging process of the eye.

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