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MyD88 Deficiency Protects Against Dry Eye–Induced Damage

PURPOSE: Dry eye disease (DED) is a multifactorial disease associated with ocular surface inflammation. Toll-like receptors (TLRs) are integral in the initiation of inflammatory signaling. Therefore, we evaluated the effect of TLR-deficiency on dry eye–related ocular surface damage and inflammation...

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Autores principales: Reins, Rose Y., Lema, Carolina, Courson, Justin, Kunnen, Carolina M. E., Redfern, Rachel L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Association for Research in Vision and Ophthalmology 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5991808/
https://www.ncbi.nlm.nih.gov/pubmed/30025110
http://dx.doi.org/10.1167/iovs.17-23397
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author Reins, Rose Y.
Lema, Carolina
Courson, Justin
Kunnen, Carolina M. E.
Redfern, Rachel L.
author_facet Reins, Rose Y.
Lema, Carolina
Courson, Justin
Kunnen, Carolina M. E.
Redfern, Rachel L.
author_sort Reins, Rose Y.
collection PubMed
description PURPOSE: Dry eye disease (DED) is a multifactorial disease associated with ocular surface inflammation. Toll-like receptors (TLRs) are integral in the initiation of inflammatory signaling. Therefore, we evaluated the effect of TLR-deficiency on dry eye–related ocular surface damage and inflammation using a mouse model of experimental dry eye (EDE). METHODS: C57BL/6 wild-type (WT), MyD88(−/−), and IL-1R(−/−) mice were exposed to EDE conditions for 5 days. Tear production was measured by phenol red thread test and ocular surface damage assessed with fluorescein staining. Corneal homogenates were obtained for matrix metalloproteinase (MMP) and cytokine expression analysis by Luminex assay and quantitative PCR. In addition, whole eyes and eyelids were dissected and goblet cells and Meibomian glands were imaged, respectively. RESULTS: Following 5 days of EDE, WT mice had extensive ocular surface staining, while MyD88(−/−) mice had no increased staining above non-EDE conditions. Similarly, MyD88(−/−) mice did not have increased corneal MMP-2, 3, or 8 concentrations, as seen with WT mice. MyD88-deficiency also resulted in decreased corneal cytokine levels. In addition, MyD88(−/−) mice had significantly lower conjunctival goblet cell counts compared with both WT (EDE) and IL-1R(−/−) (non-EDE) mice. However, there was no difference in Meibomian gland morphology between WT, IL-1R(−/−), and MyD88(−/−) mice. CONCLUSIONS: These studies demonstrate the importance of TLR signaling in dry eye development. Mice lacking TLR signaling, MyD88(−/−), were protected from EDE-induced ocular surface damage and inflammatory mediator expression, warranting further investigation into TLR inhibition as a potential therapeutic for DED.
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spelling pubmed-59918082018-06-08 MyD88 Deficiency Protects Against Dry Eye–Induced Damage Reins, Rose Y. Lema, Carolina Courson, Justin Kunnen, Carolina M. E. Redfern, Rachel L. Invest Ophthalmol Vis Sci Immunology and Microbiology PURPOSE: Dry eye disease (DED) is a multifactorial disease associated with ocular surface inflammation. Toll-like receptors (TLRs) are integral in the initiation of inflammatory signaling. Therefore, we evaluated the effect of TLR-deficiency on dry eye–related ocular surface damage and inflammation using a mouse model of experimental dry eye (EDE). METHODS: C57BL/6 wild-type (WT), MyD88(−/−), and IL-1R(−/−) mice were exposed to EDE conditions for 5 days. Tear production was measured by phenol red thread test and ocular surface damage assessed with fluorescein staining. Corneal homogenates were obtained for matrix metalloproteinase (MMP) and cytokine expression analysis by Luminex assay and quantitative PCR. In addition, whole eyes and eyelids were dissected and goblet cells and Meibomian glands were imaged, respectively. RESULTS: Following 5 days of EDE, WT mice had extensive ocular surface staining, while MyD88(−/−) mice had no increased staining above non-EDE conditions. Similarly, MyD88(−/−) mice did not have increased corneal MMP-2, 3, or 8 concentrations, as seen with WT mice. MyD88-deficiency also resulted in decreased corneal cytokine levels. In addition, MyD88(−/−) mice had significantly lower conjunctival goblet cell counts compared with both WT (EDE) and IL-1R(−/−) (non-EDE) mice. However, there was no difference in Meibomian gland morphology between WT, IL-1R(−/−), and MyD88(−/−) mice. CONCLUSIONS: These studies demonstrate the importance of TLR signaling in dry eye development. Mice lacking TLR signaling, MyD88(−/−), were protected from EDE-induced ocular surface damage and inflammatory mediator expression, warranting further investigation into TLR inhibition as a potential therapeutic for DED. The Association for Research in Vision and Ophthalmology 2018-06 /pmc/articles/PMC5991808/ /pubmed/30025110 http://dx.doi.org/10.1167/iovs.17-23397 Text en Copyright 2018 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
spellingShingle Immunology and Microbiology
Reins, Rose Y.
Lema, Carolina
Courson, Justin
Kunnen, Carolina M. E.
Redfern, Rachel L.
MyD88 Deficiency Protects Against Dry Eye–Induced Damage
title MyD88 Deficiency Protects Against Dry Eye–Induced Damage
title_full MyD88 Deficiency Protects Against Dry Eye–Induced Damage
title_fullStr MyD88 Deficiency Protects Against Dry Eye–Induced Damage
title_full_unstemmed MyD88 Deficiency Protects Against Dry Eye–Induced Damage
title_short MyD88 Deficiency Protects Against Dry Eye–Induced Damage
title_sort myd88 deficiency protects against dry eye–induced damage
topic Immunology and Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5991808/
https://www.ncbi.nlm.nih.gov/pubmed/30025110
http://dx.doi.org/10.1167/iovs.17-23397
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