Mitochondrial quality control in non-exudative age-related macular degeneration : from molecular mechanisms to structural and functional recovery

Abstract: Non-exudative age-related macular degeneration (NE-AMD) is the leading blindness cause in the elderly. Clinical and experimental evidence supports that early alterations in macular retinal pigment epithelium (RPE) mitochondria play a key role in NE-AMD-induced damage. Mitochondrial dynam...

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Autores principales: Dieguez, Hernán H., Romeo, Horacio, Alaimo, Agustina, Bernal Aguirre, Nathaly Azucena, Adán Aréan, Juan S., Álvarez, Silvia, Sciurano, Roberta, Rosenstein, Ruth E., Dorfman, Damián
Formato: Artículo
Lenguaje:Inglés
Publicado: Elsevier 2024
Materias:
CELULAS
RETINA
MITOCONDRIAS
METFORMINA
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/18267
Aporte de:
Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139-123456789-18267
record_format dspace
spelling I33-R139-123456789-182672024-06-13T08:47:03Z Mitochondrial quality control in non-exudative age-related macular degeneration : from molecular mechanisms to structural and functional recovery Dieguez, Hernán H. Romeo, Horacio Alaimo, Agustina Bernal Aguirre, Nathaly Azucena Adán Aréan, Juan S. Álvarez, Silvia Sciurano, Roberta Rosenstein, Ruth E. Dorfman, Damián CELULAS RETINA MITOCONDRIAS METFORMINA Abstract: Non-exudative age-related macular degeneration (NE-AMD) is the leading blindness cause in the elderly. Clinical and experimental evidence supports that early alterations in macular retinal pigment epithelium (RPE) mitochondria play a key role in NE-AMD-induced damage. Mitochondrial dynamics (biogenesis, fusion, fission, and mitophagy), which is under the central control of AMP-activated kinase (AMPK), in turn, determines mitochondrial quality. We have developed a NE-AMD model in C57BL/6J mice induced by unilateral superior cervical ganglionectomy (SCGx), which progressively reproduces the disease hallmarks circumscribed to the temporal region of the RPE/outer retina that exhibits several characteristics of the human macula. In this work we have studied RPE mitochondrial structure, dynamics, function, and AMPK role on these parameters’ regulation at the nasal and temporal RPE from control eyes and at an early stage of experimental NE-AMD (i.e., 4 weeks post-SCGx). Although RPE mitochondrial mass was preserved, their function, which was higher at the temporal than at the nasal RPE in control eyes, was significantly decreased at 4 weeks post-SCGx at the same region. Mitochondria were bigger, more elongated, and with denser cristae at the temporal RPE from control eyes. Exclusively at the temporal RPE, SCGx severely affected mitochondrial morphology and dynamics, together with the levels of phosphorylated AMPK (p-AMPK). AMPK activation with metformin restored RPE p-AMPK levels, and mitochondrial dynamics, structure, and function at 4 weeks post-SCGx, as well as visual function and RPE/outer retina structure at 10 weeks post-SCGx. These results demonstrate a key role of the temporal RPE mitochondrial homeostasis as an early target for NE-AMD-induced damage, and that pharmacological AMPK activation could preserve mitochondrial morphology, dynamics, and function, and, consequently, avoid the functional and structural damage induced by NE-AMD. 2024-06-11T17:19:56Z 2024-06-11T17:20:00Z 2024-06-11T17:19:56Z 2024-06-11T17:20:00Z 2024 Artículo Dorfman, D. et al. Mitochondrial quality control in non-exudative age-related macular degeneration : from molecular mechanisms to structural and functional recovery [en línea]. Free radical biology & medicine. 2024, 219. doi: 10.1016/j.freeradbiomed.2024.03.024. Disponible en: https://repositorio.uca.edu.ar/handle/123456789/18267 1873-4596 (impreso) 0891-5849 (online) https://repositorio.uca.edu.ar/handle/123456789/18267 10.1016/j.freeradbiomed.2024.03.024 eng Acceso restringido http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Elsevier Free radical biology & medicine
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic CELULAS
RETINA
MITOCONDRIAS
METFORMINA
spellingShingle CELULAS
RETINA
MITOCONDRIAS
METFORMINA
Dieguez, Hernán H.
Romeo, Horacio
Alaimo, Agustina
Bernal Aguirre, Nathaly Azucena
Adán Aréan, Juan S.
Álvarez, Silvia
Sciurano, Roberta
Rosenstein, Ruth E.
Dorfman, Damián
Mitochondrial quality control in non-exudative age-related macular degeneration : from molecular mechanisms to structural and functional recovery
topic_facet CELULAS
RETINA
MITOCONDRIAS
METFORMINA
description Abstract: Non-exudative age-related macular degeneration (NE-AMD) is the leading blindness cause in the elderly. Clinical and experimental evidence supports that early alterations in macular retinal pigment epithelium (RPE) mitochondria play a key role in NE-AMD-induced damage. Mitochondrial dynamics (biogenesis, fusion, fission, and mitophagy), which is under the central control of AMP-activated kinase (AMPK), in turn, determines mitochondrial quality. We have developed a NE-AMD model in C57BL/6J mice induced by unilateral superior cervical ganglionectomy (SCGx), which progressively reproduces the disease hallmarks circumscribed to the temporal region of the RPE/outer retina that exhibits several characteristics of the human macula. In this work we have studied RPE mitochondrial structure, dynamics, function, and AMPK role on these parameters’ regulation at the nasal and temporal RPE from control eyes and at an early stage of experimental NE-AMD (i.e., 4 weeks post-SCGx). Although RPE mitochondrial mass was preserved, their function, which was higher at the temporal than at the nasal RPE in control eyes, was significantly decreased at 4 weeks post-SCGx at the same region. Mitochondria were bigger, more elongated, and with denser cristae at the temporal RPE from control eyes. Exclusively at the temporal RPE, SCGx severely affected mitochondrial morphology and dynamics, together with the levels of phosphorylated AMPK (p-AMPK). AMPK activation with metformin restored RPE p-AMPK levels, and mitochondrial dynamics, structure, and function at 4 weeks post-SCGx, as well as visual function and RPE/outer retina structure at 10 weeks post-SCGx. These results demonstrate a key role of the temporal RPE mitochondrial homeostasis as an early target for NE-AMD-induced damage, and that pharmacological AMPK activation could preserve mitochondrial morphology, dynamics, and function, and, consequently, avoid the functional and structural damage induced by NE-AMD.
format Artículo
author Dieguez, Hernán H.
Romeo, Horacio
Alaimo, Agustina
Bernal Aguirre, Nathaly Azucena
Adán Aréan, Juan S.
Álvarez, Silvia
Sciurano, Roberta
Rosenstein, Ruth E.
Dorfman, Damián
author_facet Dieguez, Hernán H.
Romeo, Horacio
Alaimo, Agustina
Bernal Aguirre, Nathaly Azucena
Adán Aréan, Juan S.
Álvarez, Silvia
Sciurano, Roberta
Rosenstein, Ruth E.
Dorfman, Damián
author_sort Dieguez, Hernán H.
title Mitochondrial quality control in non-exudative age-related macular degeneration : from molecular mechanisms to structural and functional recovery
title_short Mitochondrial quality control in non-exudative age-related macular degeneration : from molecular mechanisms to structural and functional recovery
title_full Mitochondrial quality control in non-exudative age-related macular degeneration : from molecular mechanisms to structural and functional recovery
title_fullStr Mitochondrial quality control in non-exudative age-related macular degeneration : from molecular mechanisms to structural and functional recovery
title_full_unstemmed Mitochondrial quality control in non-exudative age-related macular degeneration : from molecular mechanisms to structural and functional recovery
title_sort mitochondrial quality control in non-exudative age-related macular degeneration : from molecular mechanisms to structural and functional recovery
publisher Elsevier
publishDate 2024
url https://repositorio.uca.edu.ar/handle/123456789/18267
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