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In vivo measurement of mitochondrial ROS production in mouse models of photoreceptor degeneration
Retinitis pigmentosa (RP) is a disease characterised by photoreceptor cell death. It can be initiated by mutations in a number of different genes, primarily affecting rods, which will die first, resulting in loss of night vision. The secondary death of cones then leads to loss of visual acuity and b...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Ltd
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10686909/ https://www.ncbi.nlm.nih.gov/pubmed/38046619 http://dx.doi.org/10.1016/j.rbc.2023.100007 |
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author | Menger, Katja E. Logan, Angela Luhmann, Ulrich F.O. Smith, Alexander J. Wright, Alan F. Ali, Robin R. Murphy, Michael P. |
author_facet | Menger, Katja E. Logan, Angela Luhmann, Ulrich F.O. Smith, Alexander J. Wright, Alan F. Ali, Robin R. Murphy, Michael P. |
author_sort | Menger, Katja E. |
collection | PubMed |
description | Retinitis pigmentosa (RP) is a disease characterised by photoreceptor cell death. It can be initiated by mutations in a number of different genes, primarily affecting rods, which will die first, resulting in loss of night vision. The secondary death of cones then leads to loss of visual acuity and blindness. We set out to investigate whether increased mitochondrial reactive oxygen species (ROS) formation, plays a role in this sequential photoreceptor degeneration. To do this we measured mitochondrial H(2)O(2) production within mouse eyes in vivo using the mass spectrometric probe MitoB. We found higher levels of mitochondrial ROS that preceded photoreceptor loss in four mouse models of RP: Pde6b(rd1/rd1); Prhp2(rds/rds); RPGR(−/−); Cln6(nclf). In contrast, there was no increase in mitochondrial ROS in loss of function models of vision loss (GNAT(−/−), OGC), or where vision loss was not due to photoreceptor death (Cln3). Upregulation of Nrf2 transcriptional activity with dimethylfumarate (DMF) lowered mitochondrial ROS in RPGR(−/−) mice. These findings have important implications for the mechanism and treatment of RP. |
format | Online Article Text |
id | pubmed-10686909 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-106869092023-12-01 In vivo measurement of mitochondrial ROS production in mouse models of photoreceptor degeneration Menger, Katja E. Logan, Angela Luhmann, Ulrich F.O. Smith, Alexander J. Wright, Alan F. Ali, Robin R. Murphy, Michael P. Redox Biochem Chem Article Retinitis pigmentosa (RP) is a disease characterised by photoreceptor cell death. It can be initiated by mutations in a number of different genes, primarily affecting rods, which will die first, resulting in loss of night vision. The secondary death of cones then leads to loss of visual acuity and blindness. We set out to investigate whether increased mitochondrial reactive oxygen species (ROS) formation, plays a role in this sequential photoreceptor degeneration. To do this we measured mitochondrial H(2)O(2) production within mouse eyes in vivo using the mass spectrometric probe MitoB. We found higher levels of mitochondrial ROS that preceded photoreceptor loss in four mouse models of RP: Pde6b(rd1/rd1); Prhp2(rds/rds); RPGR(−/−); Cln6(nclf). In contrast, there was no increase in mitochondrial ROS in loss of function models of vision loss (GNAT(−/−), OGC), or where vision loss was not due to photoreceptor death (Cln3). Upregulation of Nrf2 transcriptional activity with dimethylfumarate (DMF) lowered mitochondrial ROS in RPGR(−/−) mice. These findings have important implications for the mechanism and treatment of RP. Elsevier Ltd 2023-12 /pmc/articles/PMC10686909/ /pubmed/38046619 http://dx.doi.org/10.1016/j.rbc.2023.100007 Text en © 2023 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Menger, Katja E. Logan, Angela Luhmann, Ulrich F.O. Smith, Alexander J. Wright, Alan F. Ali, Robin R. Murphy, Michael P. In vivo measurement of mitochondrial ROS production in mouse models of photoreceptor degeneration |
title | In vivo measurement of mitochondrial ROS production in mouse models of photoreceptor degeneration |
title_full | In vivo measurement of mitochondrial ROS production in mouse models of photoreceptor degeneration |
title_fullStr | In vivo measurement of mitochondrial ROS production in mouse models of photoreceptor degeneration |
title_full_unstemmed | In vivo measurement of mitochondrial ROS production in mouse models of photoreceptor degeneration |
title_short | In vivo measurement of mitochondrial ROS production in mouse models of photoreceptor degeneration |
title_sort | in vivo measurement of mitochondrial ros production in mouse models of photoreceptor degeneration |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10686909/ https://www.ncbi.nlm.nih.gov/pubmed/38046619 http://dx.doi.org/10.1016/j.rbc.2023.100007 |
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