Proteomic approaches to understanding age-related macular degeneration.

@article{Hollyfield2003ProteomicAT,
  title={Proteomic approaches to understanding age-related macular degeneration.},
  author={J. Hollyfield and R. G. Salomon and J. Crabb},
  journal={Advances in experimental medicine and biology},
  year={2003},
  volume={533},
  pages={
          83-9
        }
}
Microdissection methods have been developed for isolating drusen and Bruch's membrane from human eyes. Comparative proteomic studies of these isolates from normal and AMD donors were pursued for clues to the biochemical pathways involved in the pathogenesis of AMD. A total of 129 potential drusen proteins were identified by LC MS/MS and immunocytochemical analyses have confirmed drusen localization for approximately 16% of the proteins. The most common drusen proteins appear to be TIMP-3… Expand
On the origin of proteins in human drusen: The meet, greet and stick hypothesis
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This work reviewed and supplemented the existing literature on the molecular composition of the retina/choroid complex and evaluated how drusen components may "meet, greet and stick" to each other and/or to structures like hydroxyapatite spherules to form macroscopic deposits in the sub-RPE-BL space. Expand
Circulating Autoantibodies in Age-Related Macular Degeneration Recognize Human Macular Tissue Antigens Implicated in Autophagy, Immunomodulation, and Protection from Oxidative Stress and Apoptosis
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Quantitative analysis of hydroxyapatite‐binding plasma proteins in genotyped individuals with late‐stage age‐related macular degeneration
TLDR
Qualitative and quantitative information is provided relating to the degree by which plasma proteins may contribute to sub‐RPE deposit formation through binding to HAP spherules and how genetic differences might contribute to deposit formation. Expand
A Proteogenomic Signature of Age-related Macular Degeneration in Blood
TLDR
A two-sample Mendelian randomization study of five proteins associated with AMD found CFHR1, CFHR5, and FUT5 to be causally related to the disease, all of which were directionally consistent with the observational estimates. Expand
Retinal pigment epithelium response to oxidant injury in the pathogenesis of early age-related macular degeneration.
TLDR
This review explores the RPE injury hypothesis, and postulates that various hormones and other plasma-derived molecules related to systemic health cofactors are implicated in this second stage of the disease. Expand
Age-related macular degeneration: the molecular link between oxidative damage, tissue-specific inflammation and outer retinal disease: the Proctor lecture.
  • J. Hollyfield
  • Biology, Medicine
  • Investigative ophthalmology & visual science
  • 2010
TLDR
The data indicating that the complement pathway is involved in AMD are unequivocal and strongly indicate that AMD has a genetic component and that inflammation plays an important role in the pathology of AMD. Expand
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References

SHOWING 1-10 OF 15 REFERENCES
Drusen proteome analysis: An approach to the etiology of age-related macular degeneration
TLDR
Data strongly support the hypothesis that oxidative injury contributes to the pathogenesis of AMD and suggest that oxidative protein modifications may have a critical role in drusen formation. Expand
A potential role for immune complex pathogenesis in drusen formation.
TLDR
The results suggest that drusen biogenesis may be a byproduct of immune responsiveness, and they implicate immune complex-mediated pathogenesis involving retinal pigmented epithelial cells as an initiating event in Drusen formation. Expand
An Integrated Hypothesis That Considers Drusen as Biomarkers of Immune-Mediated Processes at the RPE-Bruch's Membrane Interface in Aging and Age-Related Macular Degeneration
TLDR
An integrated ultrastructural, histochemical, molecular biological, and biochemical approach is described to identify specific molecular pathways associated with drusen biogenesis and invokes, for the first time, the potential for a direct role of cell- and immune-mediated processes in drusens biogenesis. Expand
Immunological and Aetiological Aspects of Macular Degeneration
TLDR
Data demonstrate the involvement of both cellular and humoral immunity in the pathogenesis of AMD, however, it remains to be determined to what degree the influence of immunity is causative or contributory in both wet and dry AMD. Expand
Evidence That Light Modulates Protein Nitration in Rat Retina *
TLDR
The identification of nitrotyrosine-containing proteins from rats maintained in the dark, under non-pathological conditions, provides the first evidence of a possible role for protein nitration in normal retinal physiology. Expand
The role of oxidative stress in the pathogenesis of age-related macular degeneration.
TLDR
The concept that AMD can be attributed to cumulative oxidative stress is enticing, but remains unproven, and the effect of nutritional antioxidant supplements on the onset and natural course of age-related macular disease is currently being evaluated. Expand
Advanced glycation end products induce angiogenesis in vivo.
TLDR
The data demonstrated that AGEs are an angiogenetic factor and that the system of AGE-induced abnormal vessels in CAMs is useful in further investigations of the mechanism of diabetic retinal angiogenesis and can also be used to provide a therapeutic model for diabetic angiopathy. Expand
Proteome survey of proliferating and differentiating rat RPE-J cells.
TLDR
The suitability of the rat derived SV-40T immortalized RPE-J cell line for identifying proteome changes associated with RPE differentiation was evaluated by surveying changes in protein expression levels and significant changes in the apparent mass and charge properties of proteins were observed. Expand
Positional cloning of the gene associated with X-linked juvenile retinoschisis
X–linked juvenile retinoschisis (RS) is a recessively inherited vitreo-retinal degeneration characterized by macular pathology and intraretinal splitting of the retina. The RS gene has been localizedExpand
Cellular Retinaldehyde-binding Protein Ligand Interactions
TLDR
The data implicate Gln-210 and Lys-221 as components of the CRALBP retinoid binding cavity and are discussed in the context of ligand interactions in structurally or functionally related proteins with known crystallographic structures. Expand
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