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Text
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<a href="http://doi.org/10.1016/j.nbd.2020.104944" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.nbd.2020.104944</a>
Pages
104944
Volume
141
ISSN
1095-953X 0969-9961
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Update Year & Number
June 2020 Update II
NEOMED College
NEOMED College of Pharmacy
NEOMED Department
NEOMED Student Publications
Department of Pharmaceutical Sciences
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Title
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MCT2 overexpression rescues metabolic vulnerability and protects retinal ganglion cells in two models of glaucoma.
Publisher
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Neurobiology of disease
Date
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2020
2020-05-15
Subject
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Glaucoma; Metabolism; Monocarboxylate transporter; Ocular hypertension; Retinal ganglion cell
Creator
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Harun-Or-Rashid Mohammad; Pappenhagen Nathaniel; Zubricky Ryan; Coughlin Lucy; Jassim Assraa Hassan; Inman Denise M
Description
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Improving cellular access to energy substrates is one strategy to overcome observed declines in energy production and utilization in the aged and pathologic central nervous system. Monocarboxylate transporters (MCTs), the movers of lactate, pyruvate, and ketone bodies into or out of a cell, are significantly decreased in the DBA/2 J mouse model of glaucoma. In order to confirm MCT decreases are disease-associated, we decreased MCT2 in the retinas of MCT2(fl/+) mice using an injection of AAV2-cre, observing significant decline in ATP production and visual evoked potential. Restoring MCT2 levels in retinal ganglion cells (RGCs) via intraocular injection of AAV2-GFP-MCT2 in two models of glaucoma, the DBA/2 J (D2), and a magnetic bead model of ocular hypertension (OHT), preserved RGCs and their function. Viral-mediated overexpression of MCT2 increased RGC density and axon number, reduced energy imbalance, and increased mitochondrial function as measured by cytochrome c oxidase and succinate dehydrogenase activity in both models of glaucoma. Ocular hypertensive mice injected with AAV2:MCT2 had significantly greater P1 amplitude as measured by pattern electroretinogram than mice with OHT alone. These findings indicate overexpression of MCT2 improves energy homeostasis in the glaucomatous visual system, suggesting that expanding energy input options for cells is a viable option to combat neurodegeneration.
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<a href="http://doi.org/10.1016/j.nbd.2020.104944" target="_blank" rel="noreferrer noopener">10.1016/j.nbd.2020.104944</a>
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journalArticle
2020
Coughlin Lucy
Department of Pharmaceutical Sciences
Glaucoma
Harun-Or-Rashid Mohammad
Inman Denise M
Jassim Assraa Hassan
journalArticle
June 2020 Update II
Metabolism
Monocarboxylate transporter
NEOMED College of Pharmacy Student
NEOMED Student Publications
Neurobiology of disease
Ocular Hypertension
Pappenhagen Nathaniel
Retinal ganglion cell
Zubricky Ryan