UMMS Affiliation
Department of Ophthalmology; Gene Therapy Center; UMass Metabolic Network
Publication Date
3-1-2016
Document Type
Article
Disciplines
Cellular and Molecular Physiology | Eye Diseases | Ophthalmology
Abstract
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.
Keywords
AMD, Gerotarget, cone degeneration, geographic atrophy, mTORC1, rod degeneration
Rights and Permissions
All Oncotarget site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
DOI of Published Version
10.18632/oncotarget.7330
Source
Oncotarget. 2016 Mar 1;7(9):9620-33. doi: 10.18632/oncotarget.7330. Link to article on publisher's site
Journal/Book/Conference Title
Oncotarget
Related Resources
PubMed ID
26883199
Repository Citation
Zieger, Marina and Punzo, Claudio, "Improved cell metabolism prolongs photoreceptor survival upon retinal-pigmented epithelium loss in the sodium iodate induced model of geographic atrophy" (2016). Open Access Articles. 2752.
https://escholarship.umassmed.edu/oapubs/2752
Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.