The Proteome of Central and Peripheral Retina with Progression of Age-Related Macular Degeneration

Ethen, Cheryl M.; Reilly, Cavan; Feng, Xu; Olsen, Timothy W.; Ferrington, Deborah A.

doi:10.1167/iovs.05-1395

Cited by 91 publications

(77 citation statements)

References 45 publications

(46 reference statements)

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“…We identified 11 protein spots whose intensity showed statistically significant variation within the day. The number of analyzed protein spots is comparable to that reported in proteomic analyses using human retinas [25] and mouse retinas [23]. We compared our results with those in the two reports and found that the expression level of heterogeneous ribonucleoprotein (hnRNP) A/B showed not only circadian (Fig.…”

Section: Overview Of 2-de Analysissupporting

confidence: 80%

Circadian proteomics of the mouse retina

et al. 2007

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The circadian clock in the retina regulates a variety of physiological phenomena such as disc shedding and melatonin release. Although these events are critical for retinal functions, it is almost unknown how the circadian clock controls the physiological rhythmicity. To gain insight into the processes, we performed a proteomic analysis using 2-DE to find proteins whose levels show circadian changes. Among 415 retinal protein spots, 11 protein spots showed circadian rhythmicity in their intensities. We performed MALDI-TOF MS and NanoLC-MS/MS analyses and identified proteins contained in the 11 spots. The proteins were related to vesicular transport, calcium-binding, protein degradation, metabolism, RNA-binding, and protein foldings, suggesting the clock-regulation of neurotransmitter release, transportation of the membrane proteins, calcium-binding capability, and so on. We also found a rhythmic phosphorylation of N-ethylmaleimide-sensitive fusion protein and identified one of the amino acid residues modified by phosphorylation. These findings provide a new perspective on the relationship between the physiological functions of the retina and the circadian clock system.

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Section: Overview Of 2-de Analysissupporting

confidence: 80%

Circadian proteomics of the mouse retina

et al. 2007

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“…In a proteomic analysis of human eyes at progressive stages of AMD, Ethen et al found differential expression of 26 proteins in the central and peripheral retina during AMD progression. Among these were several molecular chaperones whose expression decreased with AMD progression, including Hsp60 and HOP [16]. Additionally, several antioxidant enzymes and chaperones that facilitate refolding or degradation of oxidatively damaged proteins decreased in AMD eyes: copper-zinc superoxide dismutase, manganese superoxide dismutase, catalase, and Hsp27, Hsp 90, and proteasome [40].…”

Section: Er Stress In Amdmentioning

confidence: 99%

“…In fact, in their study of retinal derivative chaperones for the P23H opsin mutant, Noorwez et al found that addition of the these chaperone molecules resulted in a 1.2 to 1.3-fold increase in the total amount of wildtype opsin in cells [61]. Additionally, proteome comparison of AMD and non-AMD eyes identified 26 proteins with significant expression change [16]. These also might serve as targets to measure the effectiveness of chaperone treatment on protein expression.…”

Section: Experimental End Points For Demonstrating Chaperone Activitymentioning

confidence: 99%

“…ER stress and protein misfolding and subsequent aggregation have been implicated in a variety of other neurodegenerative diseases that share pathological features with AMD [13,14]. Proteome analysis of human retinas with AMD and murine models of retinal degeneration found altered expression of molecular chaperones ---a diverse group of proteins found in high concentration in ER, which help prevent protein aggregation by encouraging unfolded proteins to a foldingcompetent state and also function as a component of the ER-specific protein-degrading apparatus to eliminate misfolded proteins [15][16][17][18]. These and other data discussed in this review indicate that the pathogenesis of AMD may be mediated, at least in part, through ER stress and protein misfolding.…”

Section: Introductionmentioning

confidence: 99%

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Unfolding the therapeutic potential of chemical chaperones for age-related macular degeneration

Sauer

Patel

Chan

et al. 2008

Expert Review of Ophthalmology

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SUMMARYRecent studies suggest that pathological processes involved in age-related macular degeneration (AMD) might induce endoplasmic reticulum (ER) stress. Growing evidence demonstrates the ability of chemical chaperones to decrease ER stress and ameliorate ER stress-related disease phenotypes, suggesting that the field of chaperone therapy might hold novel treatments for AMD. In this review, we examine the evidence suggesting a role for ER stress in AMD. Furthermore, we discuss the use of chaperone therapy for the treatment of ER stress-associated diseases, including other neurodegenerative diseases and retinopathies. Finally, we examine strategies for identifying potential chaperone compounds and for experimentally demonstrating chaperone activity in in vitro and in vivo models of human disease.

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“…Ethen et al analyzed region specific changes in retinal protein levels in AMD donor eyes. They identified several proteins through MALDI-TOF and could detect altered concentrations of, e.g., heat shock protein 60 or aA-and aB-crystallin in AMD eyes in comparison to controls [121]. A significantly elevated level of C-reactive protein (CRP) has been found in patients with intermediate and advanced stages of AMD compared to controls [122].…”

Section: Age-related Macular Degenerationmentioning

confidence: 99%

Proteomics in ocular fluids

Grus

Joachim

Pfeiffer

2007

Proteomics Clinical Apps

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The focus of this article is to review recent techniques in proteomic analysis of ocular fluids. These fluids include tears, aqueous humor, and vitreous, they will also be compared to serum analysis. Furthermore, we attempt to summarize some disease correlated biomarkers in ocular fluids that were discovered through different proteomic techniques in eye diseases like dry eye, glaucoma, age-related macular degeneration, uveitis, or diabetic retinopathy. This review is trying to point out the importance of these biomarkers for clinical applications.

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The Proteome of Central and Peripheral Retina with Progression of Age-Related Macular Degeneration

Abstract: This study provides the first direct evidence of AMD stage- and region-specific changes in retinal protein levels and highlights potential novel, disease-related proteins and biochemical pathways for future studies of AMD.

Cited by 91 publications

References 45 publications

Circadian proteomics of the mouse retina

Circadian proteomics of the mouse retina

Unfolding the therapeutic potential of chemical chaperones for age-related macular degeneration

Proteomics in ocular fluids

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