Dataset Information

The role of inflammation in the pathogenesis of age-related macular degeneration.

ABSTRACT: Age-related macular degeneration (AMD), the leading cause of blindness in the elderly, is a complex disease to study because of the potential role of demographic, environmental, and other systemic risk factors, such as age, sex, race, light exposure, diet, smoking, and underlying cardiovascular disease which may contribute to the pathogenesis of this disease. Recently, single nucleotide polymorphisms, DNA sequence variations found within the complement Factor H gene, have been found to be strongly associated with the development of AMD in Caucasians. One single nucleotide polymorphism, Tyr402His, was associated with approximately 50% of AMD cases. We review recent developments in the molecular biology of AMD, including single nucleotide polymorphisms within the Factor H gene, which may predispose individuals to the susceptibility of AMD as well as single nucleotide polymorphisms that may confer a protective effect. Taken together these findings help to provide new insights into the central issues surrounding the pathogenesis of AMD.

SUBMITTER: Donoso LA

PROVIDER: S-EPMC4853913 | biostudies-literature | 2006 Mar-Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The role of inflammation in the pathogenesis of age-related macular degeneration.

Donoso Larry A LA Kim David D Frost Arcilee A Callahan Alston A Hageman Gregory G

Survey of ophthalmology 20060301 2

Age-related macular degeneration (AMD), the leading cause of blindness in the elderly, is a complex disease to study because of the potential role of demographic, environmental, and other systemic risk factors, such as age, sex, race, light exposure, diet, smoking, and underlying cardiovascular disease which may contribute to the pathogenesis of this disease. Recently, single nucleotide polymorphisms, DNA sequence variations found within the complement Factor H gene, have been found to be strong ...[more]

PMID: 16500214

Similar Datasets

Project description:Cell death of retinal pigment epithelium (RPE) is characterized as an essential late-stage phenomenon of dry age-related macular degeneration (AMD). The aim of this study was to elucidate the molecular mechanism underlying RPE cell death after exposure to oxidative stress, which occurs often because of the anatomical location of RPE cells. ARPE-19, an established RPE cell line, exhibited necrotic features involving poly (ADP-ribose) polymerase-1 (PARP-1) activation in response to hydrogen peroxide (H2O2). ARPE-19 cells were resistant to H2O2 when PARP-1 was depleted using siRNA or inhibited by a pharmacological inhibitor of PARP-1, olaparib. Our data suggest a causal relationship between PARP-1 activation and ARPE-19 cell death in response to H2O2. Next, we investigated downstream molecular events in PARP-1 activation. Increased mitochondrial depolarization, mitochondrial fission and alterations of the cellular energy dynamics with reduced NAD+ and ATP were observed in H2O2-treated ARPE-19 cells. H2O2-triggered mitochondrial dysfunction was inhibited by olaparib. Nevertheless, translocation of apoptosis-inducing factor (AIF), a biochemical signature for PARP-1-dependent cell death (parthanatos), was not observed in our study. Moreover, the depletion of AIF did not affect the amplitude of cell death, demonstrating the lack of a role for AIF in the death of ARPE-19 cells in response to H2O2. This feature distinguishes the type of death observed in this study from canonical parthanatos. Next, we examined the in vivo role of PARP-1 in a dry AMD animal model system. Histological analysis of the outer nuclear layer in the mouse retina revealed protection against sodium iodate (SI) following treatment with olaparib. Moreover, retina fundus and electroretinograms also confirmed such a protective effect in the SI-treated rabbit. Collectively, we report that AIF-independent PARP-1-dependent necrosis constitutes a major mechanism of RPE cell death leading to retinal degeneration in dry AMD.

Dataset Information

The role of inflammation in the pathogenesis of age-related macular degeneration.

Publications

The role of inflammation in the pathogenesis of age-related macular degeneration.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets