MCT2 overexpression rescues metabolic vulnerability and protects retinal ganglion cells in two models of glaucoma
| العنوان: | MCT2 overexpression rescues metabolic vulnerability and protects retinal ganglion cells in two models of glaucoma |
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| المؤلفون: | Nathaniel Pappenhagen, Mohammad Harun-Or-Rashid, Denise M. Inman, Ryan Zubricky, Lucy Coughlin, Assraa Hassan Jassim |
| المصدر: | Neurobiology of Disease, Vol 141, Iss, Pp 104944-(2020) Neurobiol Dis |
| بيانات النشر: | Elsevier BV, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, Retinal Ganglion Cells, 0301 basic medicine, genetic structures, Ocular hypertension, Glaucoma, Energy homeostasis, 0302 clinical medicine, Retinal ganglion cell, Axon, Monocarboxylate transporter, 0303 health sciences, biology, Chemistry, Neurodegeneration, Mitochondria, Cell biology, medicine.anatomical_structure, Neurology, Optic nerve, Female, Microglia, Monocarboxylic Acid Transporters, medicine.medical_specialty, Mice, Transgenic, Retinal ganglion, Article, lcsh:RC321-571, 03 medical and health sciences, Internal medicine, medicine, Animals, Cytochrome c oxidase, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, 030304 developmental biology, Retina, Optic Nerve, medicine.disease, eye diseases, Disease Models, Animal, Metabolism, 030104 developmental biology, Endocrinology, biology.protein, Evoked Potentials, Visual, sense organs, 030217 neurology & neurosurgery |
| الوصف: | 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/2J mouse model of glaucoma. In order to confirm MCT decreases are disease-associated, we decreased MCT2 in the retinas of MCT2fl/+ 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/2J (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.HighlightsLoss of MCT2 in retina compromises visual function and ATP production in optic nerveMCT2 overexpression preserves RGC soma and axon number in two glaucoma modelsMCT2 overexpression improves energy homeostasis in optic nerve |
| تدمد: | 0969-9961 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::362279c827cc6f737241d5c60b5c0c61 https://doi.org/10.1016/j.nbd.2020.104944 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....362279c827cc6f737241d5c60b5c0c61 |
| قاعدة البيانات: | OpenAIRE |
Full Text via ClinicalKey | تدمد: | 09699961 |
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