Systems-level analysis of age-related macular degeneration reveals global biomarkers and phenotype-specific functional networks

Abstract

Background: Age-related macular degeneration (AMD) is a leading cause of blindness that affects the central region of the retinal pigmented epithelium (RPE), choroid, and neural retina. Initially characterized by an accumulation of sub-RPE deposits, AMD leads to progressive retinal degeneration, and in advanced cases, irreversible vision loss. Although genetic analysis, animal models, and cell culture systems have yielded important insights into AMD, the molecular pathways underlying AMD's onset and progression remain poorly delineated. We sought to better understand the molecular underpinnings of this devastating disease by performing the first comparative transcriptome analysis of AMD and normal human donor eyes.

Expression and differential regulation of HLA-G isoforms in the retinal pigment epithelial cell line, ARPE-19

“…The RPE has a number of immunoregulatory functions, one of which could be expression of the non-classical human leukocyte antigen (HLA) molecule, HLA-G. Gene expression of HLA-G has been found present in the RPE/choroid of human donor eyes; however, these results have not been confirmed for protein expression, nor have the expression been credited to a specific cell type [29].…”

Transcriptome changes in age-related macular degeneration

“…The authors compared gene expression of 37 AMD eyes (divided into categories based on disease phenotype) with 31 normal eyes [14]. Expression profiling was performed for both the neural retina and the combined RPE/choroid layers of the eye using an oligonucleotide microarray platform.…”

TAK1 Inhibition Accelerates Cellular Senescence of Retinal Pigment Epithelial Cells

“…3 At an early stage of dry AMD, the RPE cells accumulate lipofuscin and participate in the formation of extracellular drusen deposits in the macular area. 4,5 The increase in drusen enhances the risk of progression to the wet form of AMD. Geographic atrophy, or advanced dry AMD, is characterized by degeneration and loss of RPE cells and their associated photoreceptors.…”

“…6 Thus, in both the early and late stages of AMD, the pathological changes target the RPE cells. 5 According to a current hypothesis on early AMD development, which focuses on oxidative stress affecting the RPE cells, it was found that RPE cells are subjected to high levels of oxidative stress from several sources, including visible light and contact with a high-oxygen environment. 7 In addition, accumulation of lipofuscin, a product of lysosomal degradation, increases in aging of RPE cells and can contribute to oxidative damage.…”