Analysis of IgG antibody patterns against retinal antigens and antibodies to α-crystallin, GFAP, and α-enolase in sera of patients with “wet” age-related macular degeneration

Joachim, Stephanie C.; Bruns, Kai; Lackner, Karl J.; Pfeiffer, Norbert; Grus, Franz H.

doi:10.1007/s00417-006-0429-9

Cited by 55 publications

(52 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, CD86 is expressed in drusen-associated dendritic cells [6], CD69 is expressed in activated leukocytes [127], and ILI41 and the elastolytic protease CTSL2 are both expressed by macrophages upon activation [128]. In addition, the up-regulation of immunoglobulin genes supports an adaptive, autoimmune response in AMD that is consistent with previous reports of immunoglobulins in drusen and drusen-associated RPE [129] as well as anti-carboxyethylpyrrole adduct antibodies [130] and anti-retinal antigen autoantibodies [131][132][133] in AMD sera.…”

Section: Discussionsupporting

confidence: 86%

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

Newman

Gallo²,

Hancox

et al. 2012

Genome Medicine

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 86%

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

Newman

Gallo²,

Hancox

et al. 2012

Genome Medicine

View full text Add to dashboard Cite

show abstract

“…Priming of RPE cells can translate to secondary effects on critical cellular processes such as phagocytosis and digestion of POS, which are increasingly affected in A/J mice with age. Another secondary effect is the production of anti-retinal antibodies to α-crystallin, GFAP, and α-enolase found in sera of ARD patients (55). Preferential activation of Stat1 has been detected in several autoimmune/ inflammatory conditions (23), and this increased significantly and exclusively in A/J mice with age.…”

Section: Methodsmentioning

confidence: 99%

Inflammatory priming predisposes mice to age-related retinal degeneration

Mustafi¹,

Maeda²,

Kohno³

et al. 2012

J. Clin. Invest.

View full text Add to dashboard Cite

Disruption of cellular processes affected by multiple genes and accumulation of numerous insults throughout life dictate the progression of age-related disorders, but their complex etiology is poorly understood. Postmitotic neurons, such as photoreceptor cells in the retina and epithelial cells in the adjacent retinal pigmented epithelium, are especially susceptible to cellular senescence, which contributes to age-related retinal degeneration (ARD). The multigenic and complex etiology of ARD in humans is reflected by the relative paucity of effective compounds for its early prevention and treatment. To understand the genetic differences that drive ARD pathogenesis, we studied A/J mice, which develop ARD more pronounced than that in other inbred mouse models. Although our investigation of consomic strains failed to identify a chromosome associated with the observed retinal deterioration, pathway analysis of RNA-Seq data from young mice prior to retinal pathological changes revealed that increased vulnerability to ARD in A/J mice was due to initially high levels of inflammatory factors and low levels of homeostatic neuroprotective factors. The genetic signatures of an uncompensated preinflammatory state and ARD progression identified here aid in understanding the susceptible genetic loci that underlie pathogenic mechanisms of age-associated disorders, including several human blinding diseases. IntroductionAge-related disorders arise from failure of tissue maintenance and repair pathways that are accelerated by certain inherited and acquired factors (1). Long-lived nondividing cells, such as neurons, have markedly reduced tolerance to damage (2), and thus exhibit the most pronounced age-related changes. Neuronal cells in the retina are an especially attractive model system to study this phenomenon, owing to their accessibility and wellunderstood physiology. Rod and cone photoreceptors are retinal neuronal cells that initiate visual perception, a function requiring a competent neighboring retinal pigmented epithelium (RPE) for their normal operation (3). In postmitotic cells such as these photoreceptor and RPE cells, cellular senescence can ensue when shed oxidized photoreceptor outer segments (POS) are inadequately phagocytosed and digested by the RPE. This results in accumulation of damaged proteins, formation of toxic metabolic byproducts, inflammatory cell invasion, and cell death. RPE cells are the most affected because, in addition to processing POS, they serve as the conduit between photoreceptors and the choroidal blood supply for metabolite exchange (4). Acquisition of senescence-associated pathology stimulates cells to secrete various factors that contribute to tissue dysfunction. Conversely, adequate clearance of such cells can delay the onset of age-related tissue pathology (5).Aging laboratory experimental animals are important models for studying age-related pathology, especially neurodegenerative disorders, which have been shown to be affected by their genetic backgrounds (6, 7). The A/J inbred mouse ...

show abstract

“…In 2006, Joachim et al identified a-crystallin, a-enolase and GFAP as IgG-targeted retinal autoantigens in patients with wet AMD, using liquid chromatography tandem mass spectroscopy (LC-MS/MS) following western blotting analysis [45]. Umeda et al revealed that titers of antibodies against annexin II, which is highly expressed in RPE cells, were highly elevated in cynomolgus monkeys with macular degeneration compared to healthy controls [46].…”

Section: Autoimmunity and Amdmentioning

confidence: 98%

Autoimmunity in retinal degeneration: Autoimmune retinopathy and age-related macular degeneration

Morohoshi

Goodwin

Ohbayashi

et al. 2009

Journal of Autoimmunity

View full text Add to dashboard Cite

Analysis of IgG antibody patterns against retinal antigens and antibodies to α-crystallin, GFAP, and α-enolase in sera of patients with “wet” age-related macular degeneration

Cited by 55 publications

References 45 publications

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

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

Inflammatory priming predisposes mice to age-related retinal degeneration

Autoimmunity in retinal degeneration: Autoimmune retinopathy and age-related macular degeneration

Contact Info

Product

Resources

About