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Thioredoxin Delays Photoreceptor Degeneration, Oxidative and Inflammation Alterations in Retinitis Pigmentosa

Retinitis pigmentosa (RP) is an inherited ocular disorder with no effective treatment. RP onset and progression trigger a cascade of retinal disorders that lead to the death of photoreceptors. After photoreceptors death, neuronal, glial and vascular remodeling can be observed in the retina. The purp...

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Autores principales: Gimeno-Hernández, Roberto, Cantó, Antolin, Fernández-Carbonell, Angel, Olivar, Teresa, Hernández-Rabaza, Vicente, Almansa, Inmaculada, Miranda, María
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785808/
https://www.ncbi.nlm.nih.gov/pubmed/33424600
http://dx.doi.org/10.3389/fphar.2020.590572
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author Gimeno-Hernández, Roberto
Cantó, Antolin
Fernández-Carbonell, Angel
Olivar, Teresa
Hernández-Rabaza, Vicente
Almansa, Inmaculada
Miranda, María
author_facet Gimeno-Hernández, Roberto
Cantó, Antolin
Fernández-Carbonell, Angel
Olivar, Teresa
Hernández-Rabaza, Vicente
Almansa, Inmaculada
Miranda, María
author_sort Gimeno-Hernández, Roberto
collection PubMed
description Retinitis pigmentosa (RP) is an inherited ocular disorder with no effective treatment. RP onset and progression trigger a cascade of retinal disorders that lead to the death of photoreceptors. After photoreceptors death, neuronal, glial and vascular remodeling can be observed in the retina. The purpose of this study was to study if thioredoxin (TRX) administration is able to decrease photoreceptor death in an animal model of RP (rd1 mouse), but also if it is able to modulate the retinal oxidative stress, glial and vascular changes that can be observed as the disease progresses. Wild type and rd1 mice received several doses of TRX. After treatment, animals were euthanized at postnatals days 11, 17, or 28. Glutathione (GSH) and other thiol compounds were determined by high performance liquid chromatography (HPLC). Glial fibrilary acidic protein (GFAP) and anti-ionized calcium binding adaptor molecule 1 (Iba1) were studied by immunohistochemistry. Vascular endothelial growth factor (VEGF) and hepatic growth factor (HGF) expression were determined by western blot. TRX administration significantly diminished cell death in rd1 mouse retinas and increased GSH retinal concentrations at postnatal day 11 (PN11). TRX was also able to reverse glial alterations at PN11 and PN17. No alterations were observed in retinal VEGF and HGF expression in rd1 mice. In conclusion, TRX treatment decreases photoreceptor death in the first stages of RP and this protective effect may be due in part to the GSH system activation and to a partially decrease in inflammation.
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spelling pubmed-77858082021-01-07 Thioredoxin Delays Photoreceptor Degeneration, Oxidative and Inflammation Alterations in Retinitis Pigmentosa Gimeno-Hernández, Roberto Cantó, Antolin Fernández-Carbonell, Angel Olivar, Teresa Hernández-Rabaza, Vicente Almansa, Inmaculada Miranda, María Front Pharmacol Pharmacology Retinitis pigmentosa (RP) is an inherited ocular disorder with no effective treatment. RP onset and progression trigger a cascade of retinal disorders that lead to the death of photoreceptors. After photoreceptors death, neuronal, glial and vascular remodeling can be observed in the retina. The purpose of this study was to study if thioredoxin (TRX) administration is able to decrease photoreceptor death in an animal model of RP (rd1 mouse), but also if it is able to modulate the retinal oxidative stress, glial and vascular changes that can be observed as the disease progresses. Wild type and rd1 mice received several doses of TRX. After treatment, animals were euthanized at postnatals days 11, 17, or 28. Glutathione (GSH) and other thiol compounds were determined by high performance liquid chromatography (HPLC). Glial fibrilary acidic protein (GFAP) and anti-ionized calcium binding adaptor molecule 1 (Iba1) were studied by immunohistochemistry. Vascular endothelial growth factor (VEGF) and hepatic growth factor (HGF) expression were determined by western blot. TRX administration significantly diminished cell death in rd1 mouse retinas and increased GSH retinal concentrations at postnatal day 11 (PN11). TRX was also able to reverse glial alterations at PN11 and PN17. No alterations were observed in retinal VEGF and HGF expression in rd1 mice. In conclusion, TRX treatment decreases photoreceptor death in the first stages of RP and this protective effect may be due in part to the GSH system activation and to a partially decrease in inflammation. Frontiers Media S.A. 2020-12-23 /pmc/articles/PMC7785808/ /pubmed/33424600 http://dx.doi.org/10.3389/fphar.2020.590572 Text en Copyright © 2020 Gimeno-Hernández, Cantó, Fernández-Carbonell, Olivar, Hernández-Rabaza, Almansa and Miranda http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Gimeno-Hernández, Roberto
Cantó, Antolin
Fernández-Carbonell, Angel
Olivar, Teresa
Hernández-Rabaza, Vicente
Almansa, Inmaculada
Miranda, María
Thioredoxin Delays Photoreceptor Degeneration, Oxidative and Inflammation Alterations in Retinitis Pigmentosa
title Thioredoxin Delays Photoreceptor Degeneration, Oxidative and Inflammation Alterations in Retinitis Pigmentosa
title_full Thioredoxin Delays Photoreceptor Degeneration, Oxidative and Inflammation Alterations in Retinitis Pigmentosa
title_fullStr Thioredoxin Delays Photoreceptor Degeneration, Oxidative and Inflammation Alterations in Retinitis Pigmentosa
title_full_unstemmed Thioredoxin Delays Photoreceptor Degeneration, Oxidative and Inflammation Alterations in Retinitis Pigmentosa
title_short Thioredoxin Delays Photoreceptor Degeneration, Oxidative and Inflammation Alterations in Retinitis Pigmentosa
title_sort thioredoxin delays photoreceptor degeneration, oxidative and inflammation alterations in retinitis pigmentosa
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785808/
https://www.ncbi.nlm.nih.gov/pubmed/33424600
http://dx.doi.org/10.3389/fphar.2020.590572
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