Proteomics of the Retinal Pigment Epithelium Reveals Altered Protein Expression at Progressive Stages of Age-Related Macular Degeneration

Nordgaard, Curtis L.; Berg, Kristin M.; Kapphahn, Rebecca J.; Reilly, Cavan; Feng, Xu; Olsen, Timothy W.; Ferrington, Deborah A.

doi:10.1167/iovs.05-0976

Cited by 136 publications

(107 citation statements)

References 45 publications

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“…Proteomic study provides direct evidence and a molecular basis for phosphorylation signaling, cytoskeletal reorganization, and apoptotic mechanisms of AMD [Nordgaard et al, 2006;Crabb et al, 2002;Ethen et al, 2006;Warburton et al, 2007]. A detailed proteome analysis of AMD supports our hypothesis that there is a positive correlation between RPE biomarkers under stress and AMD as shown in Table 1.…”

Section: Phosphorylation Signaling In the Rpesupporting

confidence: 81%

“…Other studies compared native differentiated to cultured dedifferentiated RPE cells [Alge et al, 2003;Alge et al, 2006]. Proteomics proved to be a useful tool in delineating changes in RPE with the progressive stages of AMD [Nordgaard et al, 2006;Norgaard et al, 2008], and diabetes [Decanini et al, 2007]. Also, proteomic tools were used to study changes in the vitreous humor associated with diabetic retinopathy and retinal proteins in glaucoma model [Tezel et al, 2005].…”

Section: Phosphorylation Signaling In the Rpementioning

confidence: 99%

“…However, accumulated phoshprylated crystallins may lead to pathological mechanism [den Engelsman et al, 2005]. In this context, stress-induced up-or down-regulation of crystallins is known to occur in various diseases or age-related conditions [Nordgaard et al, 2006;Ethen et al, 2006]. The functional relationship between heat-shock proteins and cytoskeletal proteins, such as intermediate filaments, vimentin and actin, is well documented [Clark et al, 2000;Xi et al, 2003].…”

Section: Amdmentioning

confidence: 99%

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New Biomarkers in the Retina and RPE Under Oxidative Stress

Jahng¹

2012

Ocular Diseases

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Section: Phosphorylation Signaling In the Rpesupporting

confidence: 81%

Section: Phosphorylation Signaling In the Rpementioning

confidence: 99%

Section: Amdmentioning

confidence: 99%

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New Biomarkers in the Retina and RPE Under Oxidative Stress

Jahng¹

2012

Ocular Diseases

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“…By comparing the ratios of positively correlated genes common to the three technologies, the authors found good correspondence between transcript ratios and protein ratios for about 75% of these genes, with approximately 25% showing poor correspondence. Thus, integration of transcriptome profiling, as presented by Newman et al ., with new and previously published proteomics surveys of AMD tissue [16-18] may resolve which transcripts are translated directly or are under post-transcriptional regulation.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome changes in age-related macular degeneration

Whitmore

Mullins

2012

BMC Med

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Age-related macular degeneration (AMD) is a debilitating, common cause of visual impairment. While the last decade has seen great progress in understanding the pathophysiology of AMD, the molecular changes that occur in eyes with AMD are still poorly understood. In the current issue of Genome Medicine, Newman and colleagues present the first systematic transcriptional profile analysis of AMD-affected tissues, providing a comprehensive set of expression data for different regions (macula versus periphery), tissues (retina versus retinal pigment epithelium (RPE)/choroid), and disease state (control versus early or advanced AMD). Their findings will serve as a foundation for additional systems-level research into the pathogenesis of this blinding disease.Please see related article: http://genomemedicine.com/content/4/2/16

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“…However, we previously found changes in a subset of HSP60 and HSP70 proteins using two-dimensional gel electrophoresis that may not be evident using Western immunoblotting, which measures total protein content. 41 The total proteasome content also increases with clinically relevant disease progression. Other investigators have reported an increase in proteasome content after exposure of cells to reactive oxygen species 45 that confers protection against oxidative damage.…”

Section: Discussionmentioning

confidence: 99%

Changes in Select Redox Proteins of the Retinal Pigment Epithelium in Age-related Macular Degeneration

Decanini

Nordgaard

Feng

et al. 2007

American Journal of Ophthalmology

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136

104

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PURPOSE-To examine changes of select reduction-oxidation (redox) sensitive proteins from human donor retinal pigment epithelium (RPE) at four stages of age-related macular degeneration (AMD). DESIGN-Experimental study.METHODS-Human donor eyes were obtained from the Minnesota Lions Eye Bank and graded using the Minnesota Grading System (MGS) into four stages that correspond to stages defined by the age-related eye disease study (AREDS). Protein content in RPE homogenates was measured using Western immunoblotting with protein-specific antibodies.RESULTS-The content of several antioxidant enzymes and specific proteins that facilitate refolding or degradation of oxidatively damaged proteins increased significantly in MGS stage 3. These proteins are involved in the primary (copper-zinc superoxide dismutase [CuZnSOD], manganese superoxide dismutase [MnSOD], and catalase) and secondary (heat shock protein [HSP] 27, HSP 90, and proteasome) defense against oxidative damage. Additionally, the insulin prosurvival receptor exhibited disease-related upregulation.CONCLUSIONS-The pattern of protein changes identified in human donor tissue graded using the MGS support the role of oxidative mechanisms in the pathogenesis and progression of AMD. The MGS uses nearly identical clinical definitions and grading criteria of AMD that are used in the AREDS, so our results apply to clinical and epidemiologic studies using similar definitions. Results from our protein analysis of human donor tissue helps to explain altered oxidative stress regulation and cell-survival pathways that occur in progressive stages of AMD.Age-related macular degeneration (amd) is the leading cause of blindness in developed countries 1-9 . The number of affected individuals in the United States alone is expected to increase nearly twofold, to approximately three million by the year 2020. 10 Fortunately, therapeutic options are improving. The use of antioxidant vitamins has been shown to delay disease progression at an intermediate stage, 11 and rapid innovation in the use of antiangiogenic therapies has resulted in new clinical methods to treat the exudative phase of AMD. 12-18 However, developing new treatment and prevention strategies targeting earlier stages of the disease requires a better understanding of the underlying disease mechanisms.Findings from the Age-Related Eye Disease Study (AREDS) clearly support the hypothesis that oxidative mechanisms play a significant role in the progression of AMD. Although several studies have shown that the intake of antioxidant-rich foods lowers the risk of AMD, 19-24 others have not supported this conclusion. 25-27 Cigarette smoking, a pro-oxidant, NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript significantly increases the risk of AMD, and this association is well supported in numerous, well-designed studies. 28-35The retinal pigment epithelium (RPE) is subject to a particularly high level of oxidative stress because of locally elevated oxygen tension, high polyunsaturated lipid con...

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Proteomics of the Retinal Pigment Epithelium Reveals Altered Protein Expression at Progressive Stages of Age-Related Macular Degeneration

Abstract: These results provide the first direct evidence of AMD stage-specific changes in human RPE protein expression and provide a basis for functional investigation of AMD that may ultimately suggest new therapeutic strategies.

Cited by 136 publications

References 45 publications

New Biomarkers in the Retina and RPE Under Oxidative Stress

New Biomarkers in the Retina and RPE Under Oxidative Stress

Transcriptome changes in age-related macular degeneration

Changes in Select Redox Proteins of the Retinal Pigment Epithelium in Age-related Macular Degeneration

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