Oxidative stress damage circumscribed to the central temporal retinal pigment epithelium in early experimental non-exudative age-related macular degeneration
Non-exudative age-related macular degeneration (NE-AMD) represents the leading cause of blindness in the elderly. The macular retinal pigment epithelium (RPE) lies in a high oxidative environment because its high metabolic demand, mitochondria concentration, reactive oxygen species levels, and macul...
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todo:paper_08915849_v131_n_p72_Dieguez2023-10-03T15:41:20Z Oxidative stress damage circumscribed to the central temporal retinal pigment epithelium in early experimental non-exudative age-related macular degeneration Dieguez, H.H. Romeo, H.E. Alaimo, A. González Fleitas, M.F. Aranda, M.L. Rosenstein, R.E. Dorfman, D. Antioxidant system Mitochondria Non-exudative age-related macular degeneration Oxidative stress Retinal pigment epithelium Superior cervical ganglion catalase copper zinc superoxide dismutase glutathione peroxidase heme oxygenase 1 manganese superoxide dismutase melanin superoxide transcription factor Nrf2 adult age related macular degeneration animal experiment animal model animal tissue antioxidant activity Article C57BL 6 mouse cell nucleus cellular parameters controlled study disorders of mitochondrial functions enzyme activity histopathology lipid peroxidation male mitochondrial mass mouse non exudative age related macular degeneration nonhuman oxidative stress pathophysiology priority journal protein analysis retina pigment epitheliopathy retinal outer nuclear layer retinal pigment epithelium superior cervical ganglionectomy Non-exudative age-related macular degeneration (NE-AMD) represents the leading cause of blindness in the elderly. The macular retinal pigment epithelium (RPE) lies in a high oxidative environment because its high metabolic demand, mitochondria concentration, reactive oxygen species levels, and macular blood flow. It has been suggested that oxidative stress-induced damage to the RPE plays a key role in NE-AMD pathogenesis. The fact that the disease limits to the macular region raises the question as to why this area is particularly susceptible. We have developed a NE-AMD model induced by superior cervical ganglionectomy (SCGx) in C57BL/6J mice, which reproduces the disease hallmarks exclusively circumscribed to the temporal region of the RPE/outer retina. The aim of this work was analyzing RPE regional differences that could explain AMD localized susceptibility. Lower melanin content, thicker basal infoldings, higher mitochondrial mass, and higher levels of antioxidant enzymes, were found in the temporal RPE compared with the nasal region. Moreover, SCGx induced a decrease in the antioxidant system, and in mitochondria mass, as well as an increase in mitochondria superoxide, lipid peroxidation products, nuclear Nrf2 and heme oxygenase-1 levels, and in the occurrence of damaged mitochondria exclusively at the temporal RPE. These findings suggest that despite the well-known differences between the human and mouse retina, it might not be NE-AMD pathophysiology which conditions the localization of the disease, but the macular RPE histologic and metabolic specific attributes that make it more susceptible to choroid alterations leading initially to a localized RPE dysfunction/damage, and secondarily to macular degeneration. © 2018 Elsevier Inc. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_08915849_v131_n_p72_Dieguez |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Antioxidant system Mitochondria Non-exudative age-related macular degeneration Oxidative stress Retinal pigment epithelium Superior cervical ganglion catalase copper zinc superoxide dismutase glutathione peroxidase heme oxygenase 1 manganese superoxide dismutase melanin superoxide transcription factor Nrf2 adult age related macular degeneration animal experiment animal model animal tissue antioxidant activity Article C57BL 6 mouse cell nucleus cellular parameters controlled study disorders of mitochondrial functions enzyme activity histopathology lipid peroxidation male mitochondrial mass mouse non exudative age related macular degeneration nonhuman oxidative stress pathophysiology priority journal protein analysis retina pigment epitheliopathy retinal outer nuclear layer retinal pigment epithelium superior cervical ganglionectomy |
| spellingShingle |
Antioxidant system Mitochondria Non-exudative age-related macular degeneration Oxidative stress Retinal pigment epithelium Superior cervical ganglion catalase copper zinc superoxide dismutase glutathione peroxidase heme oxygenase 1 manganese superoxide dismutase melanin superoxide transcription factor Nrf2 adult age related macular degeneration animal experiment animal model animal tissue antioxidant activity Article C57BL 6 mouse cell nucleus cellular parameters controlled study disorders of mitochondrial functions enzyme activity histopathology lipid peroxidation male mitochondrial mass mouse non exudative age related macular degeneration nonhuman oxidative stress pathophysiology priority journal protein analysis retina pigment epitheliopathy retinal outer nuclear layer retinal pigment epithelium superior cervical ganglionectomy Dieguez, H.H. Romeo, H.E. Alaimo, A. González Fleitas, M.F. Aranda, M.L. Rosenstein, R.E. Dorfman, D. Oxidative stress damage circumscribed to the central temporal retinal pigment epithelium in early experimental non-exudative age-related macular degeneration |
| topic_facet |
Antioxidant system Mitochondria Non-exudative age-related macular degeneration Oxidative stress Retinal pigment epithelium Superior cervical ganglion catalase copper zinc superoxide dismutase glutathione peroxidase heme oxygenase 1 manganese superoxide dismutase melanin superoxide transcription factor Nrf2 adult age related macular degeneration animal experiment animal model animal tissue antioxidant activity Article C57BL 6 mouse cell nucleus cellular parameters controlled study disorders of mitochondrial functions enzyme activity histopathology lipid peroxidation male mitochondrial mass mouse non exudative age related macular degeneration nonhuman oxidative stress pathophysiology priority journal protein analysis retina pigment epitheliopathy retinal outer nuclear layer retinal pigment epithelium superior cervical ganglionectomy |
| description |
Non-exudative age-related macular degeneration (NE-AMD) represents the leading cause of blindness in the elderly. The macular retinal pigment epithelium (RPE) lies in a high oxidative environment because its high metabolic demand, mitochondria concentration, reactive oxygen species levels, and macular blood flow. It has been suggested that oxidative stress-induced damage to the RPE plays a key role in NE-AMD pathogenesis. The fact that the disease limits to the macular region raises the question as to why this area is particularly susceptible. We have developed a NE-AMD model induced by superior cervical ganglionectomy (SCGx) in C57BL/6J mice, which reproduces the disease hallmarks exclusively circumscribed to the temporal region of the RPE/outer retina. The aim of this work was analyzing RPE regional differences that could explain AMD localized susceptibility. Lower melanin content, thicker basal infoldings, higher mitochondrial mass, and higher levels of antioxidant enzymes, were found in the temporal RPE compared with the nasal region. Moreover, SCGx induced a decrease in the antioxidant system, and in mitochondria mass, as well as an increase in mitochondria superoxide, lipid peroxidation products, nuclear Nrf2 and heme oxygenase-1 levels, and in the occurrence of damaged mitochondria exclusively at the temporal RPE. These findings suggest that despite the well-known differences between the human and mouse retina, it might not be NE-AMD pathophysiology which conditions the localization of the disease, but the macular RPE histologic and metabolic specific attributes that make it more susceptible to choroid alterations leading initially to a localized RPE dysfunction/damage, and secondarily to macular degeneration. © 2018 Elsevier Inc. |
| format |
JOUR |
| author |
Dieguez, H.H. Romeo, H.E. Alaimo, A. González Fleitas, M.F. Aranda, M.L. Rosenstein, R.E. Dorfman, D. |
| author_facet |
Dieguez, H.H. Romeo, H.E. Alaimo, A. González Fleitas, M.F. Aranda, M.L. Rosenstein, R.E. Dorfman, D. |
| author_sort |
Dieguez, H.H. |
| title |
Oxidative stress damage circumscribed to the central temporal retinal pigment epithelium in early experimental non-exudative age-related macular degeneration |
| title_short |
Oxidative stress damage circumscribed to the central temporal retinal pigment epithelium in early experimental non-exudative age-related macular degeneration |
| title_full |
Oxidative stress damage circumscribed to the central temporal retinal pigment epithelium in early experimental non-exudative age-related macular degeneration |
| title_fullStr |
Oxidative stress damage circumscribed to the central temporal retinal pigment epithelium in early experimental non-exudative age-related macular degeneration |
| title_full_unstemmed |
Oxidative stress damage circumscribed to the central temporal retinal pigment epithelium in early experimental non-exudative age-related macular degeneration |
| title_sort |
oxidative stress damage circumscribed to the central temporal retinal pigment epithelium in early experimental non-exudative age-related macular degeneration |
| url |
http://hdl.handle.net/20.500.12110/paper_08915849_v131_n_p72_Dieguez |
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