Improved cell metabolism prolongs photoreceptor survival upon retinal-pigmented epithelium loss in the sodium iodate induced model of geographic atrophy
Document Type
Journal ArticlePublication Date
2016-03-01Keywords
AMDGerotarget
cone degeneration
geographic atrophy
mTORC1
rod degeneration
Cellular and Molecular Physiology
Eye Diseases
Ophthalmology
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Age-related macular degeneration (AMD) is characterized by malfunction and loss of retinal-pigmented epithelium (RPE) cells. Because the RPE transfers nutrients from the choriocapillaris to photoreceptor (PR), PRs are affected as well. Geographic atrophy (GA) is an advanced form of AMD characterized by severe vision impairment due to RPE loss over large areas. Currently there is no treatment to delay the degeneration of nutrient deprived PRs once RPE cells die. Here we show that cell-autonomous activation of the key regulator of cell metabolism, the kinase mammalian target of rapamycin complex 1 (mTORC1), delays PR death in the sodium iodate induced model of RPE atrophy. Consistent with this finding loss of mTORC1 in cones accelerates cone death as cones fail to balance demand with supply. Interestingly, promoting rod survival does not promote cone survival in this model of RPE atrophy as both, rods and cones suffer from a sick and dying RPE. The findings suggest that activation of metabolic genes downstream of mTORC1 can serve as a strategy to prolong PR survival when RPE cells malfunction or die.Source
Oncotarget. 2016 Mar 1;7(9):9620-33. doi: 10.18632/oncotarget.7330. Link to article on publisher's siteDOI
10.18632/oncotarget.7330Permanent Link to this Item
http://hdl.handle.net/20.500.14038/39943PubMed ID
26883199Related Resources
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All Oncotarget site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.Distribution License
http://creativecommons.org/licenses/by/3.0/ae974a485f413a2113503eed53cd6c53
10.18632/oncotarget.7330
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Except where otherwise noted, this item's license is described as All Oncotarget site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.