HK2 Mediated Glycolytic Metabolism in Mouse Photoreceptors Is Not Required to Cause Late Stage Age-Related Macular Degeneration-Like Pathologies
Age-related macular degeneration (AMD) is a multifactorial disease of unclear etiology. We previously proposed that metabolic adaptations in photoreceptors (PRs) play a role in disease progression. We mimicked these metabolic adaptations in mouse PRs through deletion of the tuberous sclerosis comple...
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| Format: | Article |
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MDPI AG
2021-06-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/11/6/871 |
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| author | Shun-Yun Cheng Anneliese Malachi Joris Cipi Shan Ma Richard S. Brush Martin-Paul Agbaga Claudio Punzo |
| author_facet | Shun-Yun Cheng Anneliese Malachi Joris Cipi Shan Ma Richard S. Brush Martin-Paul Agbaga Claudio Punzo |
| author_sort | Shun-Yun Cheng |
| collection | DOAJ |
| description | Age-related macular degeneration (AMD) is a multifactorial disease of unclear etiology. We previously proposed that metabolic adaptations in photoreceptors (PRs) play a role in disease progression. We mimicked these metabolic adaptations in mouse PRs through deletion of the tuberous sclerosis complex (TSC) protein TSC1. Here, we confirm our previous findings by deletion of the other complex protein, namely TSC2, in rod photoreceptors. Similar to deletion of <i>Tsc1</i>, mice with deletion of <i>Tsc2</i> in rods develop AMD-like pathologies, including accumulation of apolipoproteins, migration of microglia, geographic atrophy, and neovascular pathologies. Subtle differences between the two mouse models, such as a significant increase in microglia activation with loss of <i>Tsc2</i>, were seen as well. To investigate the role of altered glucose metabolism in disease pathogenesis, we generated mice with simulation deletions of <i>Tsc2</i> and hexokinase-2 (<i>Hk2</i>) in rods. Although retinal lactate levels returned to normal in mice with <i>Tsc2-Hk2</i> deletion, AMD-like pathologies still developed. The data suggest that the metabolic adaptations in PRs that cause AMD-like pathologies are independent of HK2-mediated aerobic glycolysis. |
| first_indexed | 2024-03-10T10:29:48Z |
| format | Article |
| id | doaj.art-f0272ab293c743cf92c0a49dfb68b639 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T10:29:48Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-f0272ab293c743cf92c0a49dfb68b6392023-11-21T23:46:23ZengMDPI AGBiomolecules2218-273X2021-06-0111687110.3390/biom11060871HK2 Mediated Glycolytic Metabolism in Mouse Photoreceptors Is Not Required to Cause Late Stage Age-Related Macular Degeneration-Like PathologiesShun-Yun Cheng0Anneliese Malachi1Joris Cipi2Shan Ma3Richard S. Brush4Martin-Paul Agbaga5Claudio Punzo6Department of Ophthalmology and Visual Sciences, University of Massachusetts Medical School, Worcester, MA 01655, USADepartment of Ophthalmology and Visual Sciences, University of Massachusetts Medical School, Worcester, MA 01655, USADepartment of Ophthalmology and Visual Sciences, University of Massachusetts Medical School, Worcester, MA 01655, USADepartment of Ophthalmology and Visual Sciences, University of Massachusetts Medical School, Worcester, MA 01655, USADepartments of Cell Biology and Ophthalmology and the Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USADepartments of Cell Biology and Ophthalmology and the Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USADepartment of Ophthalmology and Visual Sciences, University of Massachusetts Medical School, Worcester, MA 01655, USAAge-related macular degeneration (AMD) is a multifactorial disease of unclear etiology. We previously proposed that metabolic adaptations in photoreceptors (PRs) play a role in disease progression. We mimicked these metabolic adaptations in mouse PRs through deletion of the tuberous sclerosis complex (TSC) protein TSC1. Here, we confirm our previous findings by deletion of the other complex protein, namely TSC2, in rod photoreceptors. Similar to deletion of <i>Tsc1</i>, mice with deletion of <i>Tsc2</i> in rods develop AMD-like pathologies, including accumulation of apolipoproteins, migration of microglia, geographic atrophy, and neovascular pathologies. Subtle differences between the two mouse models, such as a significant increase in microglia activation with loss of <i>Tsc2</i>, were seen as well. To investigate the role of altered glucose metabolism in disease pathogenesis, we generated mice with simulation deletions of <i>Tsc2</i> and hexokinase-2 (<i>Hk2</i>) in rods. Although retinal lactate levels returned to normal in mice with <i>Tsc2-Hk2</i> deletion, AMD-like pathologies still developed. The data suggest that the metabolic adaptations in PRs that cause AMD-like pathologies are independent of HK2-mediated aerobic glycolysis.https://www.mdpi.com/2218-273X/11/6/871AMDaerobic glycolysisglycolytic metabolismphotoreceptorsGACNV |
| spellingShingle | Shun-Yun Cheng Anneliese Malachi Joris Cipi Shan Ma Richard S. Brush Martin-Paul Agbaga Claudio Punzo HK2 Mediated Glycolytic Metabolism in Mouse Photoreceptors Is Not Required to Cause Late Stage Age-Related Macular Degeneration-Like Pathologies Biomolecules AMD aerobic glycolysis glycolytic metabolism photoreceptors GA CNV |
| title | HK2 Mediated Glycolytic Metabolism in Mouse Photoreceptors Is Not Required to Cause Late Stage Age-Related Macular Degeneration-Like Pathologies |
| title_full | HK2 Mediated Glycolytic Metabolism in Mouse Photoreceptors Is Not Required to Cause Late Stage Age-Related Macular Degeneration-Like Pathologies |
| title_fullStr | HK2 Mediated Glycolytic Metabolism in Mouse Photoreceptors Is Not Required to Cause Late Stage Age-Related Macular Degeneration-Like Pathologies |
| title_full_unstemmed | HK2 Mediated Glycolytic Metabolism in Mouse Photoreceptors Is Not Required to Cause Late Stage Age-Related Macular Degeneration-Like Pathologies |
| title_short | HK2 Mediated Glycolytic Metabolism in Mouse Photoreceptors Is Not Required to Cause Late Stage Age-Related Macular Degeneration-Like Pathologies |
| title_sort | hk2 mediated glycolytic metabolism in mouse photoreceptors is not required to cause late stage age related macular degeneration like pathologies |
| topic | AMD aerobic glycolysis glycolytic metabolism photoreceptors GA CNV |
| url | https://www.mdpi.com/2218-273X/11/6/871 |
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