Proteomics of vitreous humor of patients with exudative age-related macular degeneration.
BACKGROUND
There is absence of specific biomarkers and an incomplete understanding of the pathophysiology of exudative age-related macular degeneration (AMD).


RESULTS
Eighty-eight vitreous samples (73 from patients with treatment naïve AMD and 15 control samples from patients with idiopathic floaters) were analyzed with capillary electrophoresis coupled to mass spectrometry in this retrospective case series to define potential candidate protein markers of AMD. Nineteen proteins were found to be upregulated in vitreous of AMD patients. Most of the proteins were plasma derived and involved in biological (ion) transport, acute phase inflammatory reaction, and blood coagulation. A number of proteins have not been previously associated to AMD including alpha-1-antitrypsin, fibrinogen alpha chain and prostaglandin H2-D isomerase. Alpha-1-antitrypsin was validated in vitreous of an independent set of AMD patients using Western blot analysis. Further systems biology analysis of the data indicated that the observed proteomic changes may reflect upregulation of immune response and complement activity.


CONCLUSIONS
Proteome analysis of vitreous samples from patients with AMD, which underwent an intravitreal combination therapy including a core vitrectomy, steroids and bevacizumab, revealed apparent AMD-specific proteomic changes. The identified AMD-associated proteins provide some insight into the pathophysiological changes associated with AMD.
Department of Ophthalmology, Goethe University, Frankfurt am Main, Germany; Doheny Eye Institute, Los Angeles, California, United States of America; Department of Ophthalmology, Ruprecht Karls University, Heidelberg, Germany.
Michael Janusz
MJ
Koss
Mosaiques Diagnostics, Hannover, Germany.
Janosch
J
Hoffmann
Department of Ophthalmology, Goethe University, Frankfurt am Main, Germany.
Nauke
N
Nguyen
Doheny Eye Institute, Los Angeles, California, United States of America.
Marcel
M
Pfister
Mosaiques Diagnostics, Hannover, Germany; BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.
Harald
H
Mischak
BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.
William
W
Mullen
BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.
Holger
H
Husi
Department of General Ophthalmology, Lublin University, Poland.
Robert
R
Rejdak
Department of Ophthalmology, Goethe University, Frankfurt am Main, Germany.
Frank
F
Koch
Department of Nephrology, Endocrinology, and Transplantation Medicine Charité-Universitaetsmedizin, Berlin, Germany.
Joachim
J
Jankowski
Department of Nephrology, Endocrinology, and Transplantation Medicine Charité-Universitaetsmedizin, Berlin, Germany.
Katharina
K
Krueger
Department of Ophthalmology, Philipps University, Marburg, Germany.
Thomas
T
Bertelmann
Mosaiques Diagnostics, Hannover, Germany.
Julie
J
Klein
Mosaiques Diagnostics, Hannover, Germany; Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institut of Cardiovascular and Metabolic Disease, Toulouse, France; Université Toulouse III Paul-Sabatier, Toulouse, France.
Joost P
JP
Schanstra
Mosaiques Diagnostics, Hannover, Germany; Department of Nephrology, Endocrinology, and Transplantation Medicine Charité-Universitaetsmedizin, Berlin, Germany.
Justyna
J
Siwy
D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000068258:Bevacizumab; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005340:Fibrinogen / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism; D054834:Lipocalins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D040901:Proteomics; D013256:Steroids / Q000627:therapeutic use; D014821:Vitrectomy; D014822:Vitreous Body / Q000737:chemistry*; D057135:Wet Macular Degeneration / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D000515:alpha 1-Antitrypsin / Q000235:genetics / Q000378:metabolism
D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D054834:Lipocalins; D010446:Peptide Fragments; D013256:Steroids; D000515:alpha 1-Antitrypsin; C098000:fibrinogen alphaC; D000068258:Bevacizumab; D005340:Fibrinogen; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase