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Corneal dysfunction precedes the onset of hyperglycemia in a mouse model of diet-induced obesity
PURPOSE: The purpose of this study was to use a mouse model of diet-induced obesity to determine if corneal dysfunction begins prior to the onset of sustained hyperglycemia and if the dysfunction is ameliorated by diet reversal. METHODS: Six-week-old male C57BL/6 mice were fed a high fat diet (HFD)...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473521/ https://www.ncbi.nlm.nih.gov/pubmed/32886728 http://dx.doi.org/10.1371/journal.pone.0238750 |
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author | Hargrave, Aubrey Courson, Justin A. Pham, Vanna Landry, Paul Magadi, Sri Shankar, Pooja Hanlon, Sam Das, Apoorva Rumbaut, Rolando E. Smith, C. Wayne Burns, Alan R. |
author_facet | Hargrave, Aubrey Courson, Justin A. Pham, Vanna Landry, Paul Magadi, Sri Shankar, Pooja Hanlon, Sam Das, Apoorva Rumbaut, Rolando E. Smith, C. Wayne Burns, Alan R. |
author_sort | Hargrave, Aubrey |
collection | PubMed |
description | PURPOSE: The purpose of this study was to use a mouse model of diet-induced obesity to determine if corneal dysfunction begins prior to the onset of sustained hyperglycemia and if the dysfunction is ameliorated by diet reversal. METHODS: Six-week-old male C57BL/6 mice were fed a high fat diet (HFD) or a normal diet (ND) for 5–15 weeks. Diet reversal (DiR) mice were fed a HFD for 5 weeks, followed by a ND for 5 or 10 weeks. Corneal sensitivity was determined using aesthesiometry. Corneal cytokine expression was analyzed using a 32-plex Luminex assay. Excised corneas were prepared for immunofluorescence microscopy to evaluate diet-induced changes and wound healing. For wounding studies, mice were fed a HFD or a ND for 10 days prior to receiving a central 2mm corneal abrasion. RESULTS: After 10 days of HFD consumption, corneal sensitivity declined. By 10 weeks, expression of corneal inflammatory mediators increased and nerve density declined. While diet reversal restored nerve density and sensitivity, the corneas remained in a heightened inflammatory state. After 10 days on the HFD, corneal circadian rhythms (limbal neutrophil accumulation, epithelial cell division and Rev-erbα expression) were blunted. Similarly, leukocyte recruitment after wounding was dysregulated and accompanied by delays in wound closure and nerve recovery. CONCLUSION: In the mouse, obesogenic diet consumption results in corneal dysfunction that precedes the onset of sustained hyperglycemia. Diet reversal only partially ameliorated this dysfunction, suggesting a HFD diet may have a lasting negative impact on corneal health that is resistant to dietary therapeutic intervention. |
format | Online Article Text |
id | pubmed-7473521 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-74735212020-09-14 Corneal dysfunction precedes the onset of hyperglycemia in a mouse model of diet-induced obesity Hargrave, Aubrey Courson, Justin A. Pham, Vanna Landry, Paul Magadi, Sri Shankar, Pooja Hanlon, Sam Das, Apoorva Rumbaut, Rolando E. Smith, C. Wayne Burns, Alan R. PLoS One Research Article PURPOSE: The purpose of this study was to use a mouse model of diet-induced obesity to determine if corneal dysfunction begins prior to the onset of sustained hyperglycemia and if the dysfunction is ameliorated by diet reversal. METHODS: Six-week-old male C57BL/6 mice were fed a high fat diet (HFD) or a normal diet (ND) for 5–15 weeks. Diet reversal (DiR) mice were fed a HFD for 5 weeks, followed by a ND for 5 or 10 weeks. Corneal sensitivity was determined using aesthesiometry. Corneal cytokine expression was analyzed using a 32-plex Luminex assay. Excised corneas were prepared for immunofluorescence microscopy to evaluate diet-induced changes and wound healing. For wounding studies, mice were fed a HFD or a ND for 10 days prior to receiving a central 2mm corneal abrasion. RESULTS: After 10 days of HFD consumption, corneal sensitivity declined. By 10 weeks, expression of corneal inflammatory mediators increased and nerve density declined. While diet reversal restored nerve density and sensitivity, the corneas remained in a heightened inflammatory state. After 10 days on the HFD, corneal circadian rhythms (limbal neutrophil accumulation, epithelial cell division and Rev-erbα expression) were blunted. Similarly, leukocyte recruitment after wounding was dysregulated and accompanied by delays in wound closure and nerve recovery. CONCLUSION: In the mouse, obesogenic diet consumption results in corneal dysfunction that precedes the onset of sustained hyperglycemia. Diet reversal only partially ameliorated this dysfunction, suggesting a HFD diet may have a lasting negative impact on corneal health that is resistant to dietary therapeutic intervention. Public Library of Science 2020-09-04 /pmc/articles/PMC7473521/ /pubmed/32886728 http://dx.doi.org/10.1371/journal.pone.0238750 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication. |
spellingShingle | Research Article Hargrave, Aubrey Courson, Justin A. Pham, Vanna Landry, Paul Magadi, Sri Shankar, Pooja Hanlon, Sam Das, Apoorva Rumbaut, Rolando E. Smith, C. Wayne Burns, Alan R. Corneal dysfunction precedes the onset of hyperglycemia in a mouse model of diet-induced obesity |
title | Corneal dysfunction precedes the onset of hyperglycemia in a mouse model of diet-induced obesity |
title_full | Corneal dysfunction precedes the onset of hyperglycemia in a mouse model of diet-induced obesity |
title_fullStr | Corneal dysfunction precedes the onset of hyperglycemia in a mouse model of diet-induced obesity |
title_full_unstemmed | Corneal dysfunction precedes the onset of hyperglycemia in a mouse model of diet-induced obesity |
title_short | Corneal dysfunction precedes the onset of hyperglycemia in a mouse model of diet-induced obesity |
title_sort | corneal dysfunction precedes the onset of hyperglycemia in a mouse model of diet-induced obesity |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473521/ https://www.ncbi.nlm.nih.gov/pubmed/32886728 http://dx.doi.org/10.1371/journal.pone.0238750 |
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