PMID- 20221855
OWN - NLM
STAT- MEDLINE
DCOM- 20101008
LR  - 20220310
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Print)
IS  - 0893-7648 (Linking)
VI  - 41
IP  - 2-3
DP  - 2010 Jun
TI  - A hapten generated from an oxidation fragment of docosahexaenoic acid is 
      sufficient to initiate age-related macular degeneration.
PG  - 290-8
LID - 10.1007/s12035-010-8110-z [doi]
AB  - The protein adduct carboxyethylpyrrole (CEP) is present in age-related macular 
      degeneration (AMD) eye tissue and in the blood of AMD patients at higher levels 
      than found in age-matched non-AMD tissues. Autoantibodies to CEP are also higher 
      in AMD blood samples than in controls. To test the hypothesis that this hapten is 
      causally involved in initiating an inflammatory response in AMD, we immunized 
      C57BL/6J mice with mouse serum albumin (MSA) adducted with CEP. Immunized mice 
      develop antibodies to CEP, fix complement component-3 in Bruch's membrane, 
      accumulate drusen below the retinal pigment epithelium during aging, show 
      decreased a- and b-wave amplitudes in response to light, and develop lesions in 
      the retinal pigment epithelium mimicking geographic atrophy, the blinding 
      end-stage condition characteristic of the dry form of AMD. Inflammatory cells are 
      present in the region of lesions and may be actively involved in the pathology 
      observed. We conclude that early immunization of mice with CEP-adducted MSA 
      sensitizes these animals to the ongoing production of CEP adducts in the outer 
      retina where DHA is abundant and the conditions for oxidative damage are 
      permissive. In response to this early sensitization, the immune system mounts a 
      complement-mediated attack on the cells of the outer retina where CEP adducts are 
      formed. This animal model for AMD is the first that was developed from an 
      inflammatory signal discovered in eye tissue and blood from AMD patients. It 
      provides a novel opportunity for dissecting the early pathology of AMD and the 
      immune response contributing to this disorder. The availability of a mouse with a 
      mechanistically based AMD-like disease that progresses rapidly is highly 
      desirable. Such a model will allow for the efficient preclinical testing of the 
      much-needed therapeutics quickly and inexpensively.
FAU - Hollyfield, Joe G
AU  - Hollyfield JG
AD  - Cole Eye Institute, Cleveland Clinic Lerner College of Medicine, Cleveland, OH, 
      USA. hollyfj@ccf.org
FAU - Perez, Victor L
AU  - Perez VL
FAU - Salomon, Robert G
AU  - Salomon RG
LA  - eng
GR  - EY014240/EY/NEI NIH HHS/United States
GR  - R01 GM021249-30/GM/NIGMS NIH HHS/United States
GR  - EY014912/EY/NEI NIH HHS/United States
GR  - R56 EY014240/EY/NEI NIH HHS/United States
GR  - R01 EY014240/EY/NEI NIH HHS/United States
GR  - R01 GM021249/GM/NIGMS NIH HHS/United States
GR  - K08 EY014912/EY/NEI NIH HHS/United States
GR  - EY015638/EY/NEI NIH HHS/United States
GR  - R01 EY014240-07/EY/NEI NIH HHS/United States
GR  - R01 EY016813/EY/NEI NIH HHS/United States
GR  - R24 EY015638-05/EY/NEI NIH HHS/United States
GR  - GM21249/GM/NIGMS NIH HHS/United States
GR  - R24 EY015638/EY/NEI NIH HHS/United States
GR  - K08 EY014912-06/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100312
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
RN  - 0 (Haptens)
RN  - 0 (Pyrroles)
RN  - 0 (Serum Albumin)
RN  - 25167-62-8 (Docosahexaenoic Acids)
SB  - IM
MH  - Animals
MH  - Complement Fixation Tests
MH  - Disease Models, Animal
MH  - *Docosahexaenoic Acids/chemistry/immunology
MH  - *Haptens/adverse effects/immunology
MH  - Humans
MH  - Macular Degeneration/*chemically induced/*immunology/pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Oxidation-Reduction
MH  - *Pyrroles/adverse effects/chemistry/immunology
MH  - Retina/metabolism/pathology/ultrastructure
MH  - Serum Albumin/metabolism
PMC - PMC3844284
MID - NIHMS266792
EDAT- 2010/03/12 06:00
MHDA- 2010/10/12 06:00
PMCR- 2013/12/01
CRDT- 2010/03/12 06:00
PHST- 2009/11/04 00:00 [received]
PHST- 2010/02/15 00:00 [accepted]
PHST- 2010/03/12 06:00 [entrez]
PHST- 2010/03/12 06:00 [pubmed]
PHST- 2010/10/12 06:00 [medline]
PHST- 2013/12/01 00:00 [pmc-release]
AID - 10.1007/s12035-010-8110-z [doi]
PST - ppublish
SO  - Mol Neurobiol. 2010 Jun;41(2-3):290-8. doi: 10.1007/s12035-010-8110-z. Epub 2010 
      Mar 12.