Cargando…
Antioxidant Treatment Limits Neuroinflammation in Experimental Glaucoma
PURPOSE: Besides primary neurotoxicity, oxidative stress may compromise the glial immune regulation and shift the immune homeostasis toward neurodegenerative inflammation in glaucoma. We tested this hypothesis through the analysis of neuroinflammatory and neurodegenerative outcomes in mouse glaucoma...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Association for Research in Vision and Ophthalmology
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4855827/ https://www.ncbi.nlm.nih.gov/pubmed/27127934 http://dx.doi.org/10.1167/iovs.16-19153 |
_version_ | 1782430422050799616 |
---|---|
author | Yang, Xiangjun Hondur, Gözde Tezel, Gülgün |
author_facet | Yang, Xiangjun Hondur, Gözde Tezel, Gülgün |
author_sort | Yang, Xiangjun |
collection | PubMed |
description | PURPOSE: Besides primary neurotoxicity, oxidative stress may compromise the glial immune regulation and shift the immune homeostasis toward neurodegenerative inflammation in glaucoma. We tested this hypothesis through the analysis of neuroinflammatory and neurodegenerative outcomes in mouse glaucoma using two experimental paradigms of decreased or increased oxidative stress. METHODS: The first experimental paradigm tested the effects of Tempol, a multifunctional antioxidant, given through osmotic mini-pumps for drug delivery by constant infusion. Following a 6-week treatment period after microbead/viscoelastic injection-induced ocular hypertension, retina and optic nerve samples were analyzed for markers of oxidative stress and cytokine profiles using specific bioassays. We also analyzed a redox-sensitive transcriptional regulator of neuroinflammation, namely NF-κB. The second paradigm included a similar analysis of the effects of overloaded oxidative stress on retina and optic nerve inflammation in mice knockout for a major antioxidant enzyme (SOD1(−/−)). RESULTS: Increased antioxidant capacity and decreased protein carbonyls and HNE adducts with Tempol treatment verified the drug delivery and biological function. Among a range of cytokines measured, proinflammatory cytokines, including IL-1, IL-2, IFN-γ, and TNF-α, exhibited more than 2-fold decreased titers in Tempol-treated ocular hypertensive eyes. Antioxidant treatment also resulted in a prominent decrease in NF-κB activation in the ocular hypertensive retina and optic nerve. Although pharmacological treatment limiting the oxidative stress resulted in decreased neuroinflammation, ocular hypertension–induced neuroinflammatory responses were increased in SOD1(−/−) mice with defective antioxidant response. CONCLUSIONS: These findings support the oxidative stress–related mechanisms of neuroinflammation and the potential of antioxidant treatment as an immunomodulation strategy for neuroprotection in glaucoma. |
format | Online Article Text |
id | pubmed-4855827 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The Association for Research in Vision and Ophthalmology |
record_format | MEDLINE/PubMed |
spelling | pubmed-48558272016-10-01 Antioxidant Treatment Limits Neuroinflammation in Experimental Glaucoma Yang, Xiangjun Hondur, Gözde Tezel, Gülgün Invest Ophthalmol Vis Sci Glaucoma PURPOSE: Besides primary neurotoxicity, oxidative stress may compromise the glial immune regulation and shift the immune homeostasis toward neurodegenerative inflammation in glaucoma. We tested this hypothesis through the analysis of neuroinflammatory and neurodegenerative outcomes in mouse glaucoma using two experimental paradigms of decreased or increased oxidative stress. METHODS: The first experimental paradigm tested the effects of Tempol, a multifunctional antioxidant, given through osmotic mini-pumps for drug delivery by constant infusion. Following a 6-week treatment period after microbead/viscoelastic injection-induced ocular hypertension, retina and optic nerve samples were analyzed for markers of oxidative stress and cytokine profiles using specific bioassays. We also analyzed a redox-sensitive transcriptional regulator of neuroinflammation, namely NF-κB. The second paradigm included a similar analysis of the effects of overloaded oxidative stress on retina and optic nerve inflammation in mice knockout for a major antioxidant enzyme (SOD1(−/−)). RESULTS: Increased antioxidant capacity and decreased protein carbonyls and HNE adducts with Tempol treatment verified the drug delivery and biological function. Among a range of cytokines measured, proinflammatory cytokines, including IL-1, IL-2, IFN-γ, and TNF-α, exhibited more than 2-fold decreased titers in Tempol-treated ocular hypertensive eyes. Antioxidant treatment also resulted in a prominent decrease in NF-κB activation in the ocular hypertensive retina and optic nerve. Although pharmacological treatment limiting the oxidative stress resulted in decreased neuroinflammation, ocular hypertension–induced neuroinflammatory responses were increased in SOD1(−/−) mice with defective antioxidant response. CONCLUSIONS: These findings support the oxidative stress–related mechanisms of neuroinflammation and the potential of antioxidant treatment as an immunomodulation strategy for neuroprotection in glaucoma. The Association for Research in Vision and Ophthalmology 2016-04-29 2016-04 /pmc/articles/PMC4855827/ /pubmed/27127934 http://dx.doi.org/10.1167/iovs.16-19153 Text en 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 | Glaucoma Yang, Xiangjun Hondur, Gözde Tezel, Gülgün Antioxidant Treatment Limits Neuroinflammation in Experimental Glaucoma |
title | Antioxidant Treatment Limits Neuroinflammation in Experimental Glaucoma |
title_full | Antioxidant Treatment Limits Neuroinflammation in Experimental Glaucoma |
title_fullStr | Antioxidant Treatment Limits Neuroinflammation in Experimental Glaucoma |
title_full_unstemmed | Antioxidant Treatment Limits Neuroinflammation in Experimental Glaucoma |
title_short | Antioxidant Treatment Limits Neuroinflammation in Experimental Glaucoma |
title_sort | antioxidant treatment limits neuroinflammation in experimental glaucoma |
topic | Glaucoma |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4855827/ https://www.ncbi.nlm.nih.gov/pubmed/27127934 http://dx.doi.org/10.1167/iovs.16-19153 |
work_keys_str_mv | AT yangxiangjun antioxidanttreatmentlimitsneuroinflammationinexperimentalglaucoma AT hondurgozde antioxidanttreatmentlimitsneuroinflammationinexperimentalglaucoma AT tezelgulgun antioxidanttreatmentlimitsneuroinflammationinexperimentalglaucoma |