Department of Ophthalmology and Visual Sciences; Horae Gene Therapy Center; Li Weibo Institute for Rare Diseases Research
Cellular and Molecular Physiology | Eye Diseases | Ophthalmology
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.
AMD, CNV, GA, aerobic glycolysis, dry AMD, glycolytic metabolism, photoreceptors, wet AMD
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DOI of Published Version
Cheng SY, Malachi A, Cipi J, Ma S, Brush RS, Agbaga MP, Punzo C. HK2 Mediated Glycolytic Metabolism in Mouse Photoreceptors Is Not Required to Cause Late Stage Age-Related Macular Degeneration-Like Pathologies. Biomolecules. 2021 Jun 11;11(6):871. doi: 10.3390/biom11060871. PMID: 34208233; PMCID: PMC8230848. Link to article on publisher's site
Cheng S, Malachi A, Cipi J, Ma S, Brush RS, Agbaga M, Punzo C. (2021). HK2 Mediated Glycolytic Metabolism in Mouse Photoreceptors Is Not Required to Cause Late Stage Age-Related Macular Degeneration-Like Pathologies. Open Access Publications by UMass Chan Authors. https://doi.org/10.3390/biom11060871. Retrieved from https://escholarship.umassmed.edu/oapubs/4768
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