Desiccating environmental stress exacerbates autoimmune lacrimal keratoconjunctivitis in non-obese diabetic mice

Yoon, Kyung-Chul; Paiva, Cintia S. de; Qi, Hong; Chen, Zhuo; Farley, William J.; Li, Dequan; Stern, Michael E.; Pflugfelder, Stephen C.

doi:10.1016/j.jaut.2007.09.003

Cited by 44 publications

(33 citation statements)

References 37 publications

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“…However, NOD.B10-H2 b do not develop type I diabetes. (32,50) Our previous published studies (13) and figure 2 show that C57BL/6 mice have the same disease phenotype that naturally occurs with age, however NOD.B10.H2 b develop disease sooner, making this a useful model for aging studies.…”

Section: Discussionmentioning

confidence: 90%

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Age-related spontaneous lacrimal keratoconjunctivitis is accompanied by dysfunctional T regulatory cells

et al. 2017

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In both humans and animal models the development of Sjögren syndrome (SS) and non-SS keratoconjunctivitis sicca (KCS) increases with age. Here, we investigated the ocular surface and lacrimal gland phenotype of NOD.B10.H2b mice at 7–14, 45–50, and 96–100 weeks. Aged mice develop increased corneal permeability, CD4+ T cell infiltration and conjunctival goblet cell loss. Aged mice have lacrimal gland (LG) atrophy with increased lymphocyte infiltration and inflammatory cytokine levels. An increase in the frequency of CD4+Foxp3+ Tregs cells was observed with age in the cervical lymph node (CLN), spleen and LG. These CD4+CD25+ lose suppressive ability, while maintaining expression of Foxp3 and producing IL-17 and IFN-γ. An increase Foxp3+IL-17+ or Foxp3+IFN-γ+ was observed in the LG and LG-draining CLN. In adoptive transfer experiments, recipients of either purified Tregs or purified T effector cells from aged donors developed lacrimal keratoconjunctivitis, while recipients of young Tregs or young T effector cells failed to develop disease. Overall, these results suggest inflammatory cytokine-producing CD4+Foxp3+ cells participate in the pathogenesis of age-related ocular surface disease.

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Section: Discussionmentioning

confidence: 90%

“…These mice fail to develop insulitis and type 1 diabetes, but continue to show a mild SS-like disease. (32)…”

Section: Introductionmentioning

confidence: 99%

Age-related spontaneous lacrimal keratoconjunctivitis is accompanied by dysfunctional T regulatory cells

et al. 2017

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“…We induced EDE by subcutaneous injection of 0.5 mg/0.2 mL scopolamine hydrobromide (Sigma-Aldrich Corp.) four times a day (8 AM, 11 AM, 2 PM, and 5 PM) with exposure to an air draft and 30% ambient humidity, as described previously. 32,33 During the experiments animal behavior, and food and water intake were not restricted.…”

Section: Mouse Model Of Dry Eye and Experimental Designmentioning

confidence: 99%

Anti-Inflammatory and Antioxidative Effects of Camellia japonica on Human Corneal Epithelial Cells and Experimental Dry Eye: In Vivo and In Vitro Study

Lee

Choi

Cui

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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Citation: Lee HS, Choi J-H, Cui L, et al. Anti-inflammatory and antioxidative effects of Camellia japonica on human corneal epithelial cells and experimental dry eye: in vivo and in vitro study. Invest Ophthalmol Vis Sci. 2017;58:119658: -120758: . DOI:10.1167 PURPOSE. To analyze the anti-inflammatory and antioxidative effects of Camellia japonica (CJ) on human corneal epithelial (HCE) cells and its therapeutic effects in a mouse model of experimental dry eye (EDE). METHODS.Camellia japonica extracts of varying concentrations (0.001%, 0.01%, and 0.1%) were used to treat HCE cells. Dichlorofluorescein diacetate (DCF-DA) and dihydroethidium (DHE) assays were performed. The production of peroxiredoxin (PRX) 1-6 and manganesedependent superoxide dismutase (MnSOD) in HCE cells was assessed using Western blot analysis. Furthermore, eye drops containing 0.001%, 0.01%, or 0.1% CJ extract or a balanced salt solution (BSS) were applied to the EDE. Clinical parameters were measured 7 days after treatment. The levels of inflammatory markers and intracellular reactive oxygen species (ROS) were measured.RESULTS. Treatment with 0.01% and 0.1% CJ extracts decreased apoptosis in HCE cells. In addition, band intensities of PRX 1, 4, and 5, as well as MnSOD, after hydrogen peroxide (H 2 O 2 ) treatment showed a significant improvement after pretreatment with 0.01% and 0.1% CJ extracts. Mice treated with 0.1% CJ extract showed significantly improved clinical parameters when compared to those of the EDE control and BSS groups. A significant decrease in the levels of inflammatory markers and intracellular ROS was observed in the 0.01% and 0.1% CJ extract groups.CONCLUSIONS. Camellia japonica extracts promoted antioxidative protein expression and suppressed apoptosis in HCE cells. Furthermore, CJ extracts improved clinical signs of dry eye and reduced oxidative stress and the expression of inflammatory markers, suggesting that eye drops containing CJ extract could be used as an adjunctive treatment for dry eye.

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“…Experimental dry eye (EDE) was induced by subcutaneous injection of 0.5 mg/0.2 mL scopolamine hydrobromide (SigmaAldrich, St. Louis, MO) four times a day (8 AM, 11 AM, 2 PM, and 5 PM) with exposure to an air draft and 30% ambient humidity, as previously described. [26][27][28][29] During these experiments, the animals' behavior, food, and water intake were not restricted.…”

Section: Mouse Model Of Dry Eye and Experimental Proceduresmentioning

confidence: 99%

Therapeutic Effect of Topical Adiponectin in a Mouse Model of Desiccating Stress–Induced Dry Eye

Woo

Chung

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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PURPOSE.To investigate the therapeutic effect of topical adiponectin in a mouse model of experimental dry eye (EDE).METHODS. EDE was created by desiccating stress in 6-to 8-week old female C57BL/6 mice. Eye drops consisting of 0.0001%, 0.001%, or 0.01% adiponectin, or balanced salt solution (BSS), were applied in EDE. Tear volume and corneal irregularity score were measured at 5 and 10 days after treatment. Levels of interleukin (IL)-1b, IL-6, tumor necrosis factor (TNF)-a, interferon (IFN)-c, and monokine induced by interferon-c (MIG) were measured in the conjunctiva and lacrimal gland using a multiplex immunobead assay at 10 days. Periodic acidSchiff staining, immunohistochemistry, and flow cytometry were also performed.RESULTS. Mice treated with 0.001% or 0.01% adiponectin showed a significant improvement in tear volume and corneal irregularity compared with the EDE control and BSS-treated groups. A significant decrease in the levels of IL1b, IL-6, TNF-a, IFN-c, and MIG and staining intensity of TNFa was observed in the 0.001% and 0.01% adiponectin-treated groups, compared with the other groups, in the conjunctiva and lacrimal gland. In the 0.001% and 0.01% adiponectintreated groups, the density of conjunctival goblet cells was higher and the number of CD4þCXCR3þ T cells was lower than in the other groups. However, there were no significant differences in all parameters between the 0.0001% adiponectin and control groups.CONCLUSIONS. Topical application of adiponectin can markedly improve clinical signs and decrease inflammation in the ocular surface and lacrimal gland of EDE, suggesting that adiponectin eye drops may be used as a therapeutic agent for dry eye disease. (Invest Ophthalmol Vis Sci. 2013;54:155-162)

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Desiccating environmental stress exacerbates autoimmune lacrimal keratoconjunctivitis in non-obese diabetic mice

Cited by 44 publications

References 37 publications

Age-related spontaneous lacrimal keratoconjunctivitis is accompanied by dysfunctional T regulatory cells

Age-related spontaneous lacrimal keratoconjunctivitis is accompanied by dysfunctional T regulatory cells

Anti-Inflammatory and Antioxidative Effects of Camellia japonica on Human Corneal Epithelial Cells and Experimental Dry Eye: In Vivo and In Vitro Study

Therapeutic Effect of Topical Adiponectin in a Mouse Model of Desiccating Stress–Induced Dry Eye

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