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The Role Of The Lacrimal Functional Unit In The Pathophysiology Of Dry Eye.

M. Stern, J. Gao, K. Siemasko, R. Beuerman, S. Pflugfelder
Published 2004 · Medicine

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The majority of dry eye symptoms are due to a chronic inflammation of the lacrimal functional unit resulting in a loss of tear film integrity and normal function. This leads to a reduction in the ability of the ocular surface to respond to environmental challenges. The underlying cause of tear film dysfunction is the alteration of tear aqueous, mucin, and lipid components. This may result from a systemic autoimmune disease or a local autoimmune event. A lack of systemic androgen support to the lacrimal gland has been shown to be a facilitative factor in the initiation of this type of pathophysiology. Tear secretion is controlled by the lacrimal functional unit consisting of the ocular surface (cornea, conjunctiva, accessory lacrimal glands, and meibomian glands), the main lacrimal gland and the interconnecting innervation. If any portion of this functional unit is compromised, lacrimal gland support to the ocular surface is impeded. Factors such as neurogenic inflammation and T cell involvement in the disease pathogenesis as well as newly developed animal models of ocular surface inflammation are discussed.
This paper references
Chemokines in autoimmune lacrimal gland disease in MRL/MpJ mice.
E. Akpek (2004)
Quantitative analysis of lacrimal gland function, apoptotic figures, Fas and Fas ligand expression of lacrimal glands in dry eye patients.
K. Tsubota (2003)
Presence of nerves and their receptors in mouse and human conjunctival goblet cells.
Y. Diebold (2001)
Report of the National Eye Institute/Industry workshop on Clinical Trials in Dry Eyes.
M. Lemp (1995)
Flow cytometric analysis of conjunctival epithelium in ocular rosacea and keratoconjunctivitis sicca.
P. J. Pisella (2000)
Role of thelCAM-1/LFA-1 Pathway during the Development of Autoimmune Dacryoadenitis in an Animal Model for Sjögren’s Syndrome
M. Takahashi (1996)
Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis
R. Watanabe-Fukunaga (1992)
Androgen influence on the meibomian gland.
D. Sullivan (2000)
Flow cytometric analysis of inflammatory markers in conjunctival epithelial cells of patients with dry eyes.
F. Brignole (2000)
Sjögren's syndrome: mechanisms ofpathogenesis involve interaction of immune and neurosecretory systems
R. Fox (2002)
Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins.
T. Mosmann (1986)
Sjögren's syndrome: cytokine and Epstein-Barr viral gene expression within the conjunctival epithelium.
D. Jones (1994)
Evidence for antimuscarinic acetylcholine receptor antibody-mediated secretory dysfunction in nod mice.
K. Nguyen (2000)
Presence of α-and β-Integrin Subunits in Rabbit Lacrimal Gland Acinar Cells Cultured on a Laminin-Rich Matrix
J. Gierow (2002)
Evaluation of Subjective Assessments and Objective Diagnostic Tests for Diagnosing Tear‐Film Disorders Known to Cause Ocular Irritation
S. Pflugfelder (1998)
Altered cytokine balance in the tear fluid and conjunctiva of patients with Sjögren's syndrome keratoconjunctivitis sicca.
S. Pflugfelder (1999)
Th1 versus Th2 immune responses in autoimmune lacrimal gland disease in MRL/Mp mice.
D. Jabs (2000)
Chemokines in rapid leukocyte adhesion triggering and migration.
B. Johnston (2002)
The role of IFN-gamma in systemic lupus erythematosus: a challenge to the Th1/Th2 paradigm in autoimmunity
A. Theofilopoulos (2001)
T cell attractant chemokine expression initiates lacrimal gland destruction in nonobese diabetic mice.
J. Törnwall (1999)
Hormone replacement therapy and dry eye syndrome.
D. A. Schaumberg (2001)
Experimentally induced dry eye produces ocular surface inflammation and epithelial disease.
D. Dursun (2002)
Expression of T lymphocyte chemoattractants and activation markers in vernal keratoconjunctivitis
A. M. El-Asrar (2002)
Utilization of the non-obese diabetic (NOD) mouse as an animal model for the study of secondary Sjögren's syndrome.
M. Humphreys-Beher (1994)
The Th1/Th2 cytokine balance changes with the progress of the immunopathological lesion of Sjogren’s syndrome
D. Mitsias (2002)
Murine models of Sjögren's syndrome. Immunohistologic analysis of different strains.
D. Jabs (1988)
Impaired neurotransmitter release from lacrimal and salivary gland nerves of a murine model of Sjögren's syndrome.
D. Zoukhri (2001)
The pathology of dry eye: the interaction between the ocular surface and lacrimal glands.
M. Stern (1998)
Androgen stimulation of lacrimal gland function in mouse models of Sjögren's syndrome
D. Sullivan (1997)
The role of Th1/Th2 polarization in mucosal immunity
M. Neurath (2002)
Analysis of topical cyclosporine treatment of patients with dry eye syndrome: effect on conjunctival lymphocytes.
K. S. Kunert (2000)
Sex steroids, meibomian gland dysfunction and evaporative dry eye in Sj ögren's syndrome
D. Sullivan (2002)
Cellular Mechanisms of Neurogenic Inflammation
J. D. Richardson (2002)
Substance P activates coincident NF-AT- and NF-kappa B-dependent adhesion molecule gene expression in microvascular endothelial cells through intracellular calcium mobilization.
K. L. Quinlan (1999)
Dry eye and delayed tear clearance: "a call to arms.".
S. Pflugfelder (2002)
Expression of cell adhesion molecules in the salivary and lacrimal glands of Sjogren's syndrome
I. Saito (1993)
Impact of gender on exocrine gland inflammation in mouse models of Sjögren's syndrome.
I. Toda (1999)
Commentary to the article--low levels of sex hormone-binding globulin and testosterone are associated with smaller, denser low density lipoproteins in normoglycemic men.
A. Vermeulen (1998)
Signaling and transcription in T helper development.
K. Murphy (2000)
ICAM-1: its role in the pathophysiology of immune activation in the MRL/LPR mouse.
J. Gao (2002)
Autoantibodies against lacrimal gland M3 muscarinic acetylcholine receptors in patients with primary Sjögren's syndrome.
S. Bacman (1998)
Conjunctival T-cell subpopulations in Sjögren's and non-Sjögren's patients with dry eye.
M. Stern (2002)
Identification of α-Fodrin as a Candidate Autoantigen in Primary Sjögren's Syndrome
N. Haneji (1997)
Inhibition of NFκB Activity through Maintenance of IκBα Levels Contributes to Dihydrotestosterone-mediated Repression of the Interleukin-6 Promoter*
E. Keller (1996)
Lymphocyte Homing and Homeostasis
E. Butcher (1996)
Presence and testosterone influence on the levels of anti- and pro-inflammatory cytokines in lacrimal tissues of a mouse model of Sjögren's syndrome.
E. Rocha (1998)
Apoptosis of ocular surface cells in experimentally induced dry eye.
S. Yeh (2003)
Modulation of IL-8 and RANTES Release in Human Conjunctival Epithelial Cells: Primary Cells and Cell Line Compared and Contrasted
E. Smit (2003)
Parasympathetic innervation of the meibomian glands in rats.
M. LeDoux (2001)
GDNF family signalling in exocrine tissues: distinct roles for GDNF and neurturin in parasympathetic neuron development.
J. Rossi (2002)
Differential and Cooperative Effects of TNFα, IL-1β, and IFNγ on Human Conjunctival Epithelial Cell Receptor Expression and Chemokine Release
J. Stahl (2003)
Molecular mechanisms regulating Th1 immune responses.
S. Szabo (2003)
Effect of androgen deficiency on the human meibomian gland and ocular surface.
K. Krenzer (2000)
The neuropeptide substance P activates transcription factor NF-kappa B and kappa B-dependent gene expression in human astrocytoma cells.
K. Lieb (1997)
Hormonal Influences on the Lacrimal Gland
D. W. Warren (1994)
A mouse model of keratoconjunctivitis sicca.
D. Dursun (2002)
The role of apoptosis in the pathogenesis of canine keratoconjunctivitis sicca: the effect of topical Cyclosporin A therapy.
J. Gao (1998)
Characterisation of the normal conjunctival leukocyte population
M. Hingorani (1997)
Sjögren's syndrome in MRL/l and MRL/n mice.
R. Hoffman (1984)
Regulation of human leukocyte antigen expression in human conjunctival epithelium.
K. Tsubota (1999)
Serum soluble adhesion molecules (sICAM-1, sVCAM-1, sE-selectin) and neopterin in patients with Sjögren's syndrome.
C. Andrýs (1999)
Transforming growth factor beta-1 and beta-2 in human tear fluid.
A. Gupta (1996)
The importance of the Schirmer test with nasal stimulation.
K. Tsubota (1991)
Androgen Deficiency, Meibomian Gland Dysfunction, and Evaporative Dry Eye
D. Sullivan (2002)
Cyclosporin A is a substance P (tachykinin NK1) receptor antagonist.
B. Gitter (1995)
Localization of κ-opioid receptor mRNA in neuronal subpopulations of rat sensory ganglia and spinal cord
M. Schäfer (1994)
Human interleukin‐2 could bind to opioid receptor and induce corresponding signal transduction
Y. Wang (1996)
ICAM-1 expression predisposes ocular tissues to immune-based inflammation in dry eye patients and Sjögrens syndrome-like MRL/lpr mice.
J. Gao (2004)
Decision making in the immune system: The lineage decisions of helper T cells
K. Murphy (2002)
Aqueous Tear Production in Patients with Neurotrophic Keratitis
T. Heigle (1996)
T cell homeostasis and systemic autoimmunity.
A. Theofilopoulos (2001)
Role of proinflammatory cytokines in the impaired lacrimation associated with autoimmune xerophthalmia.
D. Zoukhri (2002)

This paper is referenced by
What We Have Learned From Animal Models of Dry Eye.
M. E. Stern (2017)
Aging of the Lachrymal Gland
H. Obata (2008)
Ocular graft-versus-host disease
Michelle Hessen (2012)
Comparative analysis of efficacy and adverse effects of tacrolimus vs cyclosporine in chronic dry eye disease: a tertiary care hospital based study
Zeenat Fatima (2018)
Trehalose efficacy in dry eye syndrome therapy in diabetic patients
N. N. Grigorieva (2016)
Discordant Dry Eye Disease (An American Ophthalmological Society Thesis).
Roni M. Shtein (2016)
Correlation Analysis of Ocular Symptoms and Signs in Patients with Dry Eye
H. Song (2017)
Dysfunkcja gruczołów Meiboma – wyzwania diagnostyczne i terapeutyczne
A. Mikita (2017)
A new approach of ocular nebulization with vitamin B12 versus oxytocin for the treatment of dry eye disease: an in vivo confocal microscopy study
J. Yang (2019)
Corneal nerves in refractive surgery and dry eye
I. Tuisku (2008)
Analysis of the relationship of the central tear meniscus area with the tear film symptomatology and stability
Carlos García-Resúa (2019)
Management of Dry Eye in Sjögren’s Syndrome
Michelle Hessen (2015)
Lid Margins: Sensitivity, Staining, Meibomian Gland Dysfunction, and Symptoms
B. Golebiowski (2012)
Prevention of Corneal Neovascularization by Adenovirus Encoding Human Vascular Endothelial Growth Factor Soluble Receptor (s-VEGFR1) in Lacrimal Gland.
L. F. Nominato (2018)
Cullen Symposium on Corneal and Ocular Surface Inflammation, 2005
A. McDermott (2005)
Evaluation of the Efficacy of 50% Autologous Serum Eye Drops in Different Ocular Surface Pathologies
F. Semeraro (2014)
The Tear Film: Anatomy and Physiology
Vikram Paranjpe (2019)
Ocular therapeutics
G. Napper (2005)
Infrared Meibography Allows Detection of Dimensional Changes in Meibomian Glands Following Intranasal Neurostimulation.
Nicholas Pondelis (2020)
Hornhautsensibilität Teil 3: Das Trockene Auge, Keratokonus, refraktive Chirurgie, Keratoplastik und systemische Erkrankungen
D. Nosch (2014)
Taller internacional sobre ojo seco (DEWS): Actualización de la enfermedad
R. Herrero-Vanrell (2007)
Dry Eye after Small Incision Lenticule Extraction (SMILE) versus Femtosecond Laser-Assisted in Situ Keratomileusis (FS-LASIK) for Myopia: A Meta-Analysis
Zeren Shen (2016)
Hyperosmolar Tears Induce Functional and Structural Alterations of Corneal Nerves: Electrophysiological and Anatomical Evidence Toward Neurotoxicity.
Harumitsu Hirata (2015)
Meibomian Gland Dysfunction Associated With Periocular Radiotherapy
Y. J. Woo (2017)
Sjögren's syndrome-like ocular surface disease in thrombospondin-1 deficient mice.
B. Turpie (2009)
Functional lacrimal gland regeneration
M. Hirayama (2017)
Prevalence and Risk Factors of Dry Eye Syndrome in the Incheon Area
Hoon Seok Jeong (2011)
A Crosslinked HA-Based Hydrogel Ameliorates Dry Eye Symptoms in Dogs
D. Williams (2013)
The cornea in keratoconjunctivitis sicca.
S. C. Pflugfelder (2020)
Phase III safety evaluation of cyclosporine 0.1% ophthalmic emulsion administered twice daily to dry eye disease patients for up to 3 years.
L. D. Barber (2005)
DDDT_A_203464 2381..2391
Jiarui Yang (2019)
The analysis of human conjunctival epithelium proteome in ocular surface diseases using impression cytology and 2D‐DIGE
J. Soria (2018)
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