Good news!
"Scientists ... reprogrammed stem cells to create models of diseased eye cells, and then analysed DNA, RNA and proteins to pinpoint the genetic clues. ...
The researchers took skin samples from 79 participants with and without the late stage of AMD, called geographic atrophy. Their skin cells were reprogrammed to revert to stem cells called induced pluripotent stem cells, and then guided with molecular signals to become retinal pigment epithelium cells, which are the cells affected in AMD. ...
Analysis of 127,600 cells revealed 439 molecular signatures associated with AMD, with 43 of those being potential new gene variants. Key pathways identified were subsequently tested within the cells and revealed differences in the energy-making mitochondria between healthy and AMD cells, rendering mitochondrial proteins as potential targets to prevent or alter the course of AMD. ..."From the abstract:
"There are currently no treatments for geographic atrophy, the advanced form of age-related macular degeneration. ... Induced pluripotent stem cells generated from patients with geographic atrophy and healthy individuals were differentiated to retinal pigment epithelium. Integrating transcriptional profiles of 127,659 retinal pigment epithelium cells generated from 43 individuals with geographic atrophy and 36 controls with genotype data, we identify 445 expression quantitative trait loci in cis that are asssociated with disease status and specific to retinal pigment epithelium subpopulations. Transcriptomics and proteomics approaches identify molecular pathways significantly upregulated in geographic atrophy, including in mitochondrial functions, metabolic pathways and extracellular cellular matrix reorganization. Five significant protein quantitative trait loci that regulate protein expression in the retinal pigment epithelium and in geographic atrophy are identified - two of which share variants with cis- expression quantitative trait loci, including proteins involved in mitochondrial biology and neurodegeneration. Investigation of mitochondrial metabolism confirms mitochondrial dysfunction as a core constitutive difference of the retinal pigment epithelium from patients with geographic atrophy. This study uncovers important differences in retinal pigment epithelium homeostasis associated with geographic atrophy."
Transcriptomic and proteomic retinal pigment epithelium signatures of age-related macular degeneration (open access)
Fig. 1: Generation of RPE from iPSCs, identification, and characterization of RPE subpopulations
No comments:
Post a Comment