HK2 Mediated Glycolytic Metabolism in Mouse Photoreceptors Is Not Required to Cause Late Stage Age-Related Macular Degeneration-Like Pathologies.
HK2 Mediated Glycolytic Metabolism in Mouse Photoreceptors Is Not Required to Cause Late Stage Age-Related Macular Degeneration-Like Pathologies.
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DOI：
10.3390/biom11060871
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发表时间：
2021-06-11
期刊：
影响因子：
5.5
通讯作者：
Punzo C
中科院分区：
文献类型：
--
作者：
Cheng SY;Malachi A;Cipi J;Ma S;Brush RS;Agbaga MP;Punzo C
视网膜相关性黄斑变性（AMD）是一种病因不明的多因素疾病。我们以前提出，光感受器（PR）的代谢适应在疾病进展中发挥作用。我们通过删除结节性硬化症复合体（TSC）蛋白TSC 1来模拟小鼠PR中的这些代谢适应。在这里，我们证实了我们以前的研究结果删除的其他复杂的蛋白质，即TSC 2，在杆光感受器。与Tsc 1缺失相似，视杆细胞中Tsc 2缺失的小鼠出现AMD样病变，包括载脂蛋白积聚、小胶质细胞迁移、地图状萎缩和新生血管病变。还观察到两种小鼠模型之间的细微差异，例如小胶质细胞活化的显著增加以及Tsc 2的丢失。为了研究葡萄糖代谢改变在疾病发病机制中的作用，我们产生了在视杆细胞中模拟缺失Tsc 2和己糖激酶-2（Hk 2）的小鼠。尽管在Tsc 2-Hk 2缺失的小鼠中视网膜乳酸水平恢复正常，但仍然发生AMD样病理。这些数据表明，PR中导致AMD样病变的代谢适应与HK 2介导的有氧糖酵解无关。
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 Tsc1, mice with deletion of Tsc2 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 Tsc2, were seen as well. To investigate the role of altered glucose metabolism in disease pathogenesis, we generated mice with simulation deletions of Tsc2 and hexokinase-2 (Hk2) in rods. Although retinal lactate levels returned to normal in mice with Tsc2-Hk2 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.
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影响因子：
11.4
作者：
Ferrington DA;Ebeling MC;Kapphahn RJ;Terluk MR;Fisher CR;Polanco JR;Roehrich H;Leary MM;Geng Z;Dutton JR;Montezuma SR
通讯作者：
Montezuma SR
影响因子：
8.1
作者：
Ferrara D;Seddon JM
通讯作者：
Seddon JM
影响因子：
4.4
作者：
Curcio CA
通讯作者：
Curcio CA
影响因子：
4.4
作者：
Curcio CA
通讯作者：
Curcio CA
DOI：
10.1085/jgp.58.3.225
发表时间：
1971-09
期刊：
The Journal of general physiology
影响因子：
--
作者：
Bownds D;Gordon-Walker A;Gaide-Huguenin AC;Robinson W
通讯作者：
Robinson W