Identification of anti-retinal antibodies in patients with age-related macular degeneration

Experimental and Molecular Pathology

Volume 93, Issue 2, October 2012, Pages 193-199

  (Article)

Morohoshi, K.^abc, 

Ohbayashi, M.^b, 

Patel, N.^d, 

Chong, V.^e, 

Bird, A.C.^f, 

Ono, S.J.^bc 

 

^a  Department of Ophthalmology, Tokyo Medical and Dental University, Tokyo, Japan
^b  Department of Ophthalmology, Emory University School of Medicine and Emory Eye Center, Dobbs Ocular Immunology Laboratories, Atlanta, GA, United States
^c  Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital, Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, United States 

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Abstract

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in industrial counties. Recent findings indicate that the autoimmunity is involved in the pathogenesis of the disease. However, there is no autoantibody biomarker applied in a clinical setting for diagnosis and prognosis of AMD.In order to reveal retinal antigens targeted by serum IgG from AMD patients, mouse retinal tissue proteins were separated by 2-dimensional electrophoresis and the proteins in the immunoblots that were specific for dry and wet AMD patients IgG were identified by LC-MS/MS.Retinol-binding protein 3 and aldolase C (ALDOC) were mainly recognized by IgG form wet AMD patients. Pyruvate kinase M2 (PKM2) was targeted by both dry and wet AMD and level of anti-PKM2 IgG antibody was correlated best with the stage of AMD. Expression of ALDOC and PKM2 was decreased in mouse retina from aging whereas PKM2 deposit on RPE was increased in aged mice.Our data demonstrate that sera of AMD patients contain autoantibodies against retinal proteins and anti-PKM2 IgG serves as a biomarker for diagnosis and prognosis of AMD. Further investigation of the association of anti-retinal antibody level with expression level of antigens in retina will be needed to reveal the disease pathogenesis. © 2012 Elsevier Inc.

Author keywords

Age-related macular degeneration; Aldolase; Anti-retinal antibody; Autoantibody profile; Pyruvate kinase

Indexed keywords

EMTREE drug terms: aldolase c; autoantibody; fructose bisphosphate aldolase; immunoglobulin G; immunoglobulin G antibody; pyruvate kinase; pyruvate kinase M2; retina antibody; retinol binding protein; retinol binding protein 3; unclassified drug

EMTREE medical terms: adult; aged; animal tissue; article; clinical article; controlled study; enzyme linked immunosorbent assay; female; human; immunoblotting; immunoglobulin blood level; immunohistochemistry; immunoreactivity; liquid chromatography; male; mass spectrometry; mouse; nonhuman; pathogenesis; protein expression; retina; retina macula age related degeneration; reverse transcription polymerase chain reaction; separation technique; two dimensional electrophoresis; Western blotting

MeSH: Aged; Aged, 80 and over; Animals; Autoantibodies; Autoantigens; Biological Markers; Female; Fructose-Bisphosphate Aldolase; Geographic Atrophy; Humans; Immunoglobulin G; Male; Mice; Prognosis; Pyruvate Kinase; Retina; Retinol-Binding Proteins; Wet Macular Degeneration
Medline is the source for the MeSH terms of this document.

Chemicals and CAS Registry Numbers: fructose bisphosphate aldolase, 9024-52-6; immunoglobulin G, 97794-27-9; pyruvate kinase, 9001-59-6;Autoantibodies; Autoantigens; Biological Markers; Fructose-Bisphosphate Aldolase, 4.1.2.13; Immunoglobulin G; Pyruvate Kinase, 2.7.1.40; Retinol-Binding Proteins

ISSN: 00144800 CODEN: EXMPASource Type: Journal Original language: English

DOI: 10.1016/j.yexmp.2012.03.007 PubMed ID: 22465421Document Type: Article

References (35)

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• 
  1

  Ahn, B.-Y., Song, E.-S., Cho, Y.J., Kwon, O.W., Kim, J.K., Lee, N.G.

  Identification of an anti-aldolase autoantibody as a diagnostic marker for diabetic retinopathy by immunoproteomic analysis
  (2006) Proteomics, 6 (4), pp. 1200-1209. Cited 30 times.
  doi: 10.1002/pmic.200500457
  

  • View at Publisher
• 
  2

  Ambati, J., Ambati, B.K., Yoo, S.H., Ianchulev, S., Adamis, A.P.

  Age-related macular degeneration: Etiology, pathogenesis, and therapeutic strategies
  (2003) Survey of Ophthalmology, 48 (3), pp. 257-293. Cited 568 times.
  doi: 10.1016/S0039-6257(03)00030-4
  

  • View at Publisher
• 
  3

  Ashizawa, K., Willingham, M.C., Liang, C.-M., Cheng, S.-Y.

  In vivo regulation of monomer-tetramer conversion of pyruvate kinase subtype M2 by glucose is mediated via fructose 1,6-bisphosphate
  (1991) Journal of Biological Chemistry, 266 (25), pp. 16842-16846. Cited 69 times.
  

  • View at Publisher
• 
  4

  Avichezer, D., Silver, P.B., Chan, C.-C., Wiggert, B., Caspi, R.R.

  Identification of a new epitope of human IRBP that induces autoimmune uveoretinitis in mice of the H-2b haplotype
  (2000) Investigative Ophthalmology and Visual Science, 41 (1), pp. 127-131. Cited 91 times.
  

  • View at Publisher
• 
  5

  Braus, B.K., Hauck, S.M., Amann, B., Heinrich, C., Fritsche, J., Köstlin, R., Deeg, C.A.

  Neuron-specific enolase antibodies in patients with sudden acquired retinal degeneration syndrome
  (2008) Veterinary Immunology and Immunopathology, 124 (1-2), pp. 177-183. Cited 10 times.
  doi: 10.1016/j.vetimm.2008.02.020
  

  • View at Publisher
• 
  6

  Butterfield, D.A., Poon, H.F., St. Clair, D., Keller, J.N., Pierce, W.M., Klein, J.B., Markesbery, W.R.

  Redox proteomics identification of oxidatively modified hippocampal proteins in mild cognitive impairment: Insights into the development of Alzheimer's disease
  (2006) Neurobiology of Disease, 22 (2), pp. 223-232. Cited 220 times.
  doi: 10.1016/j.nbd.2005.11.002
  

  • View at Publisher
• 
  7

  Caffe, A.R., Von Schantz, M., Szel, A., Voogd, J., Van Veen, T.

  Distribution of Purkinje cell-specific Zebrin-II/aldolase C immunoreactivity in the mouse, rat, rabbit, and human retina
  (1994) Journal of Comparative Neurology, 348 (2), pp. 291-297. Cited 15 times.
  

  • View at Publisher
• 
  8

  Cano, M., Thimmalappula, R., Fujihara, M., Nagai, N., Sporn, M., Wang, A.L., Neufeld, A.H., (...), Handa, J.T.
  , 50, pp. 652-64.
  Cigarette smoking, oxidative stress, the anti-oxidant response through Nrf2 signaling, and Age-related Macular Degeneration. Vision Research
  

  •  
• 
  9

  Clemons, T.E., Milton, R.C., Klein, R., Seddon, J.M., Ferris, F.L.
  Risk factors for the incidence of advanced age-related macular degeneration in the Age-Related Eye Disease Study (AREDS) AREDS report no. 19
  (2005) Ophthalmology, 112, pp. 533-539. Cited 188 times.
  

  •  
• 
  10

  Crabb, J.W., Miyagi, M., Gu, X., Shadrach, K., West, K.A., Sakaguchi, H., Kamei, M., (...), Hollyfield, J.G.

  Drusen proteome analysis: An approach to the etiology of age-related macular degeneration
  (2002) Proceedings of the National Academy of Sciences of the United States of America, 99 (23), pp. 14682-14687. Cited 620 times.
  doi: 10.1073/pnas.222551899
  

  • View at Publisher
• 
  11

  Deeg, C.A., Raith, A.J., Amann, B., Crabb, J.W., Thurau, S.R., Hauck, S.M., Ueffing, M., (...), Stangassinger, M.

  CRALBP is a highly prevalent autoantigen for human autoimmune uveitis
  (2007) Clinical and Developmental Immunology, 2007, art. no. 39245. Cited 29 times.
  doi: 10.1155/2007/39245
  

  • View at Publisher
• 
  12

  Donoso, L.A., Kim, D., Frost, A., Callahan, A., Hageman, G.

  The role of inflammation in the pathogenesis of age-related macular degeneration
  (2006) Survey of Ophthalmology, 51 (2), pp. 137-152. Cited 306 times.
  doi: 10.1016/j.survophthal.2005.12.001
  

  • View at Publisher
• 
  13

  Edwards, A.O., Ritter III, R., Abel, K.J., Manning, A., Panhuysen, C., Farrer, L.A.

  Complement factor H polymorphism and age-related macular degeneration
  (2005) Science, 308 (5720), pp. 421-424. Cited 1590 times.
  doi: 10.1126/science.1110189
  

  • View at Publisher
• 
  14

  Gu, X., Meer, S.G., Miyagi, M., Rayborn, M.E., Hollyfield, J.G., Crabb, J.W., Salomon, R.G.

  Carboxyethylpyrrole Protein Adducts and Autoantibodies, Biomarkers for Age-related Macular Degeneration
  (2003) Journal of Biological Chemistry, 278 (43), pp. 42027-42035. Cited 174 times.
  doi: 10.1074/jbc.M305460200
  

  • View at Publisher
• 
  15

  Gu, J., Pauer, G.J.T., Yue, X., Narendra, U., Sturgill, G.M., Bena, J., Gu, X., (...), Crabb, J.W.

  Proteomic and genomic biomarkers for age-related macular degeneration
  (2010) Advances in Experimental Medicine and Biology, 664, pp. 411-417. Cited 12 times.
  ISBN: 978-144191398-2
  doi: 10.1007/978-1-4419-1399-9_47
  

  • View at Publisher
• 
  16

  Gupta, V., Bamezai, R.N.K.

  Human pyruvate kinase M2: A multifunctional protein
  (2010) Protein Science, 19 (11), pp. 2031-2044. Cited 63 times.
  http://onlinelibrary.wiley.com/doi/10.1002/pro.505/pdf
  doi: 10.1002/pro.505
  

  • View at Publisher
• 
  17

  Heckenlively, J.R., Jordan, B.L., Aptsiauri, N.

  Association of antiretinal antibodies and cystoid macular edema in patients with retinitis pigmentosa
  (1999) American Journal of Ophthalmology, 127 (5), pp. 565-573. Cited 77 times.
  doi: 10.1016/S0002-9394(98)00446-2
  

  • View at Publisher
• 
  18

  Hollyfield, J.G., Bonilha, V.L., Rayborn, M.E., Yang, X., Shadrach, K.G., Lu, L., Ufret, R.L., (...), Perez, V.L.

  Oxidative damage-induced inflammation initiates age-related macular degeneration
  (2008) Nature Medicine, 14 (2), pp. 194-198. Cited 349 times.
  doi: 10.1038/nm1709
  

  • View at Publisher
• 
  19

  Jager, R.D., Mieler, W.F., Miller, J.W.

  Age-related macular degeneration
  (2008) New England Journal of Medicine, 358 (24), pp. 2606-2617+2544. Cited 594 times.
  http://content.nejm.org/cgi/reprint/358/24/2606.pdf
  doi: 10.1056/NEJMra0801537
  

  • View at Publisher
• 
  20

  Joachim, S.C., Bruns, K., Lackner, K.J., Pfeiffer, N., Grus, F.H.
  Analysis of IgG antibody patterns against retinal antigens and antibodies to alpha-crystallin, GFAP, and alpha-enolase in sera of patients with "wet" age-related macular degeneration
  (2006) Graefe's Archive for Clinical and Experimental Ophthalmology. Cited 2 times.
  

  •  
• 
  21

  Kaarniranta, K., Salminen, A., Haapasalo, A., Soininen, H., Hiltunen, M.

  Age-related macular degeneration (AMD): Alzheimer's disease in the eye?
  (2011) Journal of Alzheimer's Disease, 24 (4), pp. 615-631. Cited 80 times.
  doi: 10.3233/JAD-2011-101908
  

  • View at Publisher
• 
  22

  Liao, W.-L., Turko, I.V.

  Accumulation of large protein fragments in prematurely senescent ARPE-19 cells
  (2009) Investigative Ophthalmology and Visual Science, 50 (10), pp. 4992-4997. Cited 5 times.
  http://www.iovs.org/cgi/reprint/50/10/4992
  doi: 10.1167/iovs.09-3671
  

  • View at Publisher
• 
  23

  Mamczur, P., Mazurek, J., Rakus, D.

  Ubiquitous presence of gluconeogenic regulatory enzyme, fructose-1,6-bisphosphatase, within layers of rat retina.
  (2010) Cell and tissue research, 341 (2), pp. 213-221. Cited 2 times.
  

  • View at Publisher
• 
  24

  Morohoshi, K., Goodwin, A.M., Ohbayashi, M., Ono, S.J.

  Autoimmunity in retinal degeneration: Autoimmune retinopathy and age-related macular degeneration
  (2009) Journal of Autoimmunity, 33 (3-4), pp. 247-254. Cited 39 times.
  doi: 10.1016/j.jaut.2009.09.003
  

  • View at Publisher
• 
  25

  Morohoshi, K., Patel, N., Ohbayashi, M., Chong, V., Grossniklaus, H.E., Bird, A.C., Ono, S.J.

  Serum autoantibody biomarkers for age-related macular degeneration and possible regulators of neovascularization
  (2012) Experimental and Molecular Pathology, 92 (1), pp. 64-73. Cited 23 times.
  doi: 10.1016/j.yexmp.2011.09.017
  

  • View at Publisher
• 
  26

  Ohguro, H., Yokoi, Y., Ohguro, I., Mamiya, K., Ishikawa, F., Yamazaki, H., Metoki, T., (...), Nakazawa, M.

  Clinical and immunologic aspects of cancer-associated retinopathy
  (2004) American Journal of Ophthalmology, 137 (6), pp. 1117-1119. Cited 51 times.
  doi: 10.1016/j.ajo.2004.01.010
  

  • View at Publisher
• 
  27

  Ohno-Matsui, K.

  Parallel findings in age-related macular degeneration and Alzheimer's disease
  (2011) Progress in Retinal and Eye Research, 30 (4), pp. 217-238. Cited 81 times.
  doi: 10.1016/j.preteyeres.2011.02.004
  

  • View at Publisher
• 
  28

  Patel, N., Ohbayashi, M., Nugent, A.K., Ramchand, K., Toda, M., Chau, K.-Y., Bunce, C., (...), Chong, V.

  Circulating anti-retinal antibodies as immune markers in age-related macular degeneration
  (2005) Immunology, 115 (3), pp. 422-430. Cited 62 times.
  doi: 10.1111/j.1365-2567.2005.02173.x
  

  • View at Publisher
• 
  29

  Perluigi, M., Di Domenico, F., Giorgi, A., Schininà, M.E., Coccia, R., Cini, C., Bellia, F., (...), Calabrese, V.

  Redox proteomics in aging rat brain: Involvement of mitochondrial reduced glutathione status and mitochondrial protein oxidation in the aging process
  (2010) Journal of Neuroscience Research, 88 (16), pp. 3498-3507. Cited 52 times.
  doi: 10.1002/jnr.22500
  

  • View at Publisher
• 
  30

  Rein, D.B., Wittenborn, J.S., Zhang, X., Honeycutt, A.A., Lesesne, S.B., Saaddine, J.

  Forecasting age-related macular degeneration through the year 2050: The potential impact of new treatments
  (2009) Archives of Ophthalmology, 127 (4), pp. 533-540. Cited 131 times.
  http://archopht.ama-assn.org/cgi/reprint/127/4/533
  doi: 10.1001/archophthalmol.2009.58
  

  • View at Publisher
• 
  31

  Seddon, J.M., Ajani, U.A., Mitchell, B.D.

  Familial aggregation of age-related maculopathy
  (1997) American Journal of Ophthalmology, 123 (2), pp. 199-206. Cited 276 times.
  

  • View at Publisher
• 
  32

  Steták, A., Veress, R., Ovádi, J., Csermely, P., Kéri, G., Ullrich, A.

  Nuclear translocation of the tumor marker pyruvate kinase M2 induces programmed cell death
  (2007) Cancer Research, 67 (4), pp. 1602-1608. Cited 102 times.
  doi: 10.1158/0008-5472.CAN-06-2870
  

  • View at Publisher
• 
  33

  Tanito, M., Haniu, H., Elliott, M.H., Singh, A.K., Matsumoto, H., Anderson, R.E.

  Identification of 4-hydroxynonenal-modified retinal proteins induced by photooxidative stress prior to retinal degeneration
  (2006) Free Radical Biology and Medicine, 41 (12), pp. 1847-1859. Cited 43 times.
  doi: 10.1016/j.freeradbiomed.2006.09.012
  

  • View at Publisher
• 
  34

  Thornton, J., Edwards, R., Mitchell, P., Harrison, R.A., Buchan, I., Kelly, S.P.

  Smoking and age-related macular degeneration: A review of association
  (2005) Eye, 19 (9), pp. 935-944. Cited 247 times.
  doi: 10.1038/sj.eye.6701978
  

  • View at Publisher
• 
  35

  Umeda, S., Suzuki, M.T., Okamoto, H., Ono, F., Mizota, A., Terao, K., Yoshikawa, Y., (...), Iwata, T.

  Molecular composition of drusen and possible involvement of anti-retinal autoimmunity in two different forms of macular degeneration in cynomolgus monkey (Macaca fascicularis)
  (2005) FASEB Journal, 19 (12), pp. 1683-1685. Cited 92 times.
  doi: 10.1096/fj.05-3525fje
  

  • View at Publisher

  Ono, S.J.; University of Cincinnati, 2614 McMicken Circle, 210 Van Wormer Hall, PO Box 210097, Cincinnati, OH 45221-0097, United States; email:santa.ono@uc.edu
© Copyright 2012 Elsevier B.V., All rights reserved. © MEDLINE® is the source for the MeSH terms of this document.