| Literature DB >> 28132833 |
Janmeet S Saini1, Barbara Corneo2, Justine D Miller3, Thomas R Kiehl3, Qingjie Wang3, Nathan C Boles3, Timothy A Blenkinsop4, Jeffrey H Stern3, Sally Temple5.
Abstract
Age-related macular degeneration (AMD) affects the retinal pigment epithelium (RPE), a cell monolayer essential for photoreceptor survival, and is the leading cause of vision loss in the elderly. There are no disease-altering therapies for dry AMD, which is characterized by accumulation of subretinal drusen deposits and complement-driven inflammation. We report the derivation of human-induced pluripotent stem cells (hiPSCs) from patients with diagnosed AMD, including two donors with the rare ARMS2/HTRA1 homozygous genotype. The hiPSC-derived RPE cells produce several AMD/drusen-related proteins, and those from the AMD donors show significantly increased complement and inflammatory factors, which are most exaggerated in the ARMS2/HTRA1 lines. Using a panel of AMD biomarkers and candidate drug screening, combined with transcriptome analysis, we discover that nicotinamide (NAM) ameliorated disease-related phenotypes by inhibiting drusen proteins and inflammatory and complement factors while upregulating nucleosome, ribosome, and chromatin-modifying genes. Thus, targeting NAM-regulated pathways is a promising avenue for developing therapeutics to combat AMD.Entities:
Keywords: age-related macular degeneration; aging; complement; drusen; human induced pluripotent stem cells; nicotinamide; retina; retinal pigment epithelium
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Year: 2017 PMID： 28132833 PMCID： PMC5419856 DOI： 10.1016/j.stem.2016.12.015
Source DB: PubMed Journal: Cell Stem Cell ISSN： 1875-9777 Impact factor: 24.633