UMMS Affiliation

Department of Ophthalmology; Gene Therapy Center; UMass Metabolic Network

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.

Rights and Permissions

Citation: Oncotarget. 2016 Mar 1;7(9):9620-33. doi: 10.18632/oncotarget.7330. Link to article on publisher's site

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

Related Resources

Link to Article in PubMed

Keywords

AMD, Gerotarget, cone degeneration, geographic atrophy, mTORC1, rod degeneration

Journal Title

Oncotarget

PubMed ID

26883199

Creative Commons License

Creative Commons Attribution 3.0 License
This work is licensed under a Creative Commons Attribution 3.0 License.

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