Dry Eye Disease

Stevenson, William; Chauhan, Sunil; Dana, Reza

doi:10.1001/archophthalmol.2011.364

Cited by 499 publications

(283 citation statements)

References 119 publications

(119 reference statements)

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“…Desiccating stress, factors that disrupt tear film stability and increase tear osmolarity, can induce ocular surface damage and initiate an inflammatory cascade that generates innate and adaptive immune responses (Stevenson et al 2012). In our study, transiently increased IL-12 expression was noted after exposure to desiccating stress.…”

Section: Discussionmentioning

confidence: 99%

Macrophage Phenotype in the Ocular Surface of Experimental Murine Dry Eye Disease

You

Coursey

Bian

et al. 2015

Arch. Immunol. Ther. Exp.

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To evaluate the phenotype of macrophages in the cornea and conjunctiva of C57BL/6 mice with induced experimental dry eye. C57BL/6 mice exposed to desiccating stress (DS) were evaluated at 1, 5, and 10 days and C57BL/6 mice maintained in non-stressed environment were used as controls. Whole eyes and adnexa were excised for histology or used for gene expression analysis. Location and phenotype of macrophages infiltrating the cornea and conjunctiva was evaluated by immunofluorescence analysis. Quantitative polymerase chain reaction evaluated macrophage markers and T cell-related and inflammatory cytokine expression in cornea and conjunctiva. Immunofluorescence staining demonstrated that macrophages reside in the conjunctiva of control and dry eye mice and their number did not change with DS. Real-time RT-PCR demonstrated that the level of M1 macrophage marker, iNOS, increased prominently in the conjunctiva at DS 10 days. In contrast, there was a non-significant decrease of the M2 marker Arg1 with DS. The levels of inflammatory cytokine, IL-12a mRNA transcript in the conjunctiva increased significantly at DS1 and decreased at DS5, while levels of IL-18 were significantly increased at DS 10. Macrophages reside in the ocular surface tissues of C57BL/6 mice. Although the number of macrophages in the conjunctiva does not change, evidence of inflammatory M1 activation after desiccating stress was observed. Better understanding of phagocyte diversity and activation in dry eye disease provide a basis for the development of phagocyte-targeted therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

Macrophage Phenotype in the Ocular Surface of Experimental Murine Dry Eye Disease

You

Coursey

Bian

et al. 2015

Arch. Immunol. Ther. Exp.

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“…The standard model of desiccating environmental stress was used to induce immune-driven dry eye disease (20, 26–28). Briefly, mice were placed in cages with a perforated screen walls and exposed to continuous airflow from fans in a low humidity (20–30%) cubicle.…”

Section: Methodsmentioning

confidence: 99%

Female-Specific Downregulation of Tissue Polymorphonuclear Neutrophils Drives Impaired Regulatory T Cell and Amplified Effector T Cell Responses in Autoimmune Dry Eye Disease

Gao

Min

Zhang

et al. 2015

The Journal of Immunology

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Immune-driven dry eye disease primarily affects women; the cause for this sex-specific prevalence is unknown. PMN have distinct phenotypes that drive inflammation but also regulate lymphocytes and are the rate-limiting cell for generating anti-inflammatory lipoxin A4 (LXA4). Estrogen regulates the LXA4 circuit to induce delayed female-specific wound healing in the cornea. However, the role of PMN in dry eye disease remains unexplored. We discovered a LXA4-producing tissue-PMN population in the corneal limbus, lacrimal glands and cervical lymph nodes of healthy male and female mice. These tissue-PMN, unlike inflammatory-PMN, expressed a highly amplified LXA4 circuit and were sex-specifically regulated during immune-driven dry eye disease. Desiccating stress in females, unlike in males, triggered a remarkable decrease in lymph node PMN and LXA4 formation that remained depressed during dry eye disease. Depressed lymph node PMN and LXA4 in females correlated with an increase in T effector cells (TH1 and TH17), a decrease in regulatory T cells (Treg) and increased dry eye pathogenesis. Antibody depletion of tissue-PMN abrogated LXA4 formation in lymph nodes, caused a marked increase in TH1 and TH17 and decrease in Treg cells. To establish an immune regulatory role for PMN-derived LXA4 in dry eye females were treated with LXA4. LXA4 treatment markedly inhibited TH1 and TH17 and amplified Treg cells in draining lymph nodes, while reducing dry eye pathogenesis. These results identify female-specific regulation of LXA4-producing tissue-PMN as a potential key factor in aberrant T effector cell activation and initiation of immune-driven dry eye disease.

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“…Dry eye is increasingly recognized as an immune-based inflammatory condition. Mouse dry eye models have shown that exposure of the ocular surface to a desiccating environment activates innate inflammatory pathways and promotes an adaptive immune response with infiltration of the conjunctiva and lacrimal gland by Th1 and Th17 cells (4)(5)(6)(7)(8). One theory for the generation of autoreactive CD4 + T cells is that dry eye disrupts ocular surface immune tolerance.…”

Section: Introductionmentioning

confidence: 99%