Retinal cholesterol metabolism is perturbated in response to experimental glaucoma in the rat
Alterations of cholesterol metabolism have been described for many neurodegenerative pathologies, such as Alzheimer’s disease in the brain and age-related macular degeneration in the retina. Recent evidence suggests that glaucoma, which is characterized by the progressive death of retinal ganglion c...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8916636/?tool=EBI |
| _version_ | 1818137541338988544 |
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| author | Elise Léger-Charnay Ségolène Gambert Lucy Martine Elisabeth Dubus Marie-Annick Maire Bénédicte Buteau Tristan Morala Vincent Gigot Alain M. Bron Lionel Bretillon Elodie A. Y. Masson |
| author_facet | Elise Léger-Charnay Ségolène Gambert Lucy Martine Elisabeth Dubus Marie-Annick Maire Bénédicte Buteau Tristan Morala Vincent Gigot Alain M. Bron Lionel Bretillon Elodie A. Y. Masson |
| author_sort | Elise Léger-Charnay |
| collection | DOAJ |
| description | Alterations of cholesterol metabolism have been described for many neurodegenerative pathologies, such as Alzheimer’s disease in the brain and age-related macular degeneration in the retina. Recent evidence suggests that glaucoma, which is characterized by the progressive death of retinal ganglion cells, could also be associated with disruption of cholesterol homeostasis. In the present study we characterized cholesterol metabolism in a rat model of laser-induced intraocular hypertension, the main risk factor for glaucoma. Sterol levels were measured using gas-chromatography and cholesterol-related gene expression using quantitative RT-PCR at various time-points. As early as 18 hours after the laser procedure, genes implicated in cholesterol biosynthesis and uptake were upregulated (+49% and +100% for HMG-CoA reductase and LDLR genes respectively, vs. naive eyes) while genes involved in efflux were downregulated (-26% and -37% for ApoE and CYP27A1 genes, respectively). Cholesterol and precursor levels were consecutively elevated 3 days post-laser (+14%, +40% and +194% for cholesterol, desmosterol and lathosterol, respectively). Interestingly, counter-regulatory mechanisms were transcriptionally activated following these initial dysregulations, which were associated with the restoration of retinal cholesterol homeostasis, favorable to ganglion cell viability, one month after the laser-induced ocular hypertension. In conclusion, we report here for the first time that ocular hypertension is associated with transient major dynamic changes in retinal cholesterol metabolism. |
| first_indexed | 2024-12-11T09:57:56Z |
| format | Article |
| id | doaj.art-32bdb84376764ca7a2b10a5f13bcfd6a |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T09:57:56Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-32bdb84376764ca7a2b10a5f13bcfd6a2022-12-22T01:12:12ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01173Retinal cholesterol metabolism is perturbated in response to experimental glaucoma in the ratElise Léger-CharnaySégolène GambertLucy MartineElisabeth DubusMarie-Annick MaireBénédicte ButeauTristan MoralaVincent GigotAlain M. BronLionel BretillonElodie A. Y. MassonAlterations of cholesterol metabolism have been described for many neurodegenerative pathologies, such as Alzheimer’s disease in the brain and age-related macular degeneration in the retina. Recent evidence suggests that glaucoma, which is characterized by the progressive death of retinal ganglion cells, could also be associated with disruption of cholesterol homeostasis. In the present study we characterized cholesterol metabolism in a rat model of laser-induced intraocular hypertension, the main risk factor for glaucoma. Sterol levels were measured using gas-chromatography and cholesterol-related gene expression using quantitative RT-PCR at various time-points. As early as 18 hours after the laser procedure, genes implicated in cholesterol biosynthesis and uptake were upregulated (+49% and +100% for HMG-CoA reductase and LDLR genes respectively, vs. naive eyes) while genes involved in efflux were downregulated (-26% and -37% for ApoE and CYP27A1 genes, respectively). Cholesterol and precursor levels were consecutively elevated 3 days post-laser (+14%, +40% and +194% for cholesterol, desmosterol and lathosterol, respectively). Interestingly, counter-regulatory mechanisms were transcriptionally activated following these initial dysregulations, which were associated with the restoration of retinal cholesterol homeostasis, favorable to ganglion cell viability, one month after the laser-induced ocular hypertension. In conclusion, we report here for the first time that ocular hypertension is associated with transient major dynamic changes in retinal cholesterol metabolism.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8916636/?tool=EBI |
| spellingShingle | Elise Léger-Charnay Ségolène Gambert Lucy Martine Elisabeth Dubus Marie-Annick Maire Bénédicte Buteau Tristan Morala Vincent Gigot Alain M. Bron Lionel Bretillon Elodie A. Y. Masson Retinal cholesterol metabolism is perturbated in response to experimental glaucoma in the rat PLoS ONE |
| title | Retinal cholesterol metabolism is perturbated in response to experimental glaucoma in the rat |
| title_full | Retinal cholesterol metabolism is perturbated in response to experimental glaucoma in the rat |
| title_fullStr | Retinal cholesterol metabolism is perturbated in response to experimental glaucoma in the rat |
| title_full_unstemmed | Retinal cholesterol metabolism is perturbated in response to experimental glaucoma in the rat |
| title_short | Retinal cholesterol metabolism is perturbated in response to experimental glaucoma in the rat |
| title_sort | retinal cholesterol metabolism is perturbated in response to experimental glaucoma in the rat |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8916636/?tool=EBI |
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