PMID- 24334446
OWN - NLM
STAT- MEDLINE
DCOM- 20140225
LR  - 20230701
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 55
IP  - 1
DP  - 2014 Jan 13
TI  - Fcgamma receptor upregulation is associated with immune complex inflammation in the 
      mouse retina and early age-related macular degeneration.
PG  - 247-58
LID - 10.1167/iovs.13-11821 [doi]
AB  - PURPOSE: Several lines of evidence suggest the involvement of antibodies and 
      immune complex inflammation in AMD, a blinding disease with a strong inflammatory 
      component. To examine this further, we developed a novel experimental mouse model 
      of retinal inflammation and evaluated whether inflammation associated with immune 
      complex formation was present in eyes of AMD donors. METHODS: A localized immune 
      complex-mediated reaction was induced in the retina of wild-type (WT), Fc 
      receptor gamma chain-deficient (gamma(-/-)), and C1q-deficient (C1q(-/-)) mice, and donor 
      eyes were obtained after death from donors with early or wet AMD and from healthy 
      control subjects. The presence of immune complexes, Fcgamma receptors (FcgammaRs), and 
      markers of macrophage/microglia activation was investigated by 
      immunohistochemistry. RESULTS: In WT and C1q(-/-) mice, immune complex deposition 
      in the retina led to a robust inflammatory response with activation of microglia, 
      recruitment of myeloid cells, and increased expression of FcgammaRI through FcgammaRIV 
      and major histocompatibility complex class II. This response was not observed in 
      gamma(-/-) mice lacking activating FcgammaRs. We found that early AMD was associated with 
      deposition of IgG, C1q, and membrane attack complex in the choriocapillaris and 
      with increased numbers of CD45+ cells expressing FcgammaRIIa and FcgammaRIIb. 
      Furthermore, FcgammaRIIa and FcgammaRIIb were observed in eyes of donors with wet AMD. 
      CONCLUSIONS: Our studies suggest that immune complexes may contribute to AMD 
      pathogenesis through interaction of IgG with FcgammaRs and might inform about 
      possible adverse effects associated with therapeutic antibodies.
FAU - Murinello, Salome
AU  - Murinello S
AD  - Centre for Biological Sciences, University of Southampton, Southampton General 
      Hospital, Southampton, United Kingdom.
FAU - Mullins, Robert F
AU  - Mullins RF
FAU - Lotery, Andrew J
AU  - Lotery AJ
FAU - Perry, V Hugh
AU  - Perry VH
FAU - Teeling, Jessica L
AU  - Teeling JL
LA  - eng
GR  - WT_/Wellcome Trust/United Kingdom
GR  - R01 EY017451/EY/NEI NIH HHS/United States
GR  - EY-017451/EY/NEI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140113
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Receptors, IgG)
SB  - IM
MH  - Animals
MH  - Disease Models, Animal
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Humans
MH  - *Immunity, Innate
MH  - Immunohistochemistry
MH  - Inflammation/*genetics/immunology
MH  - Macular Degeneration/*genetics/immunology/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Receptors, IgG/biosynthesis/*genetics/immunology
MH  - *Up-Regulation
PMC - PMC3891269
OTO - NOTNLM
OT  - Fc receptor
OT  - immune complex
OT  - immunoglobulin
OT  - inflammation
OT  - macular degeneration
EDAT- 2013/12/18 06:00
MHDA- 2014/02/26 06:00
PMCR- 2014/07/01
CRDT- 2013/12/17 06:00
PHST- 2013/12/17 06:00 [entrez]
PHST- 2013/12/18 06:00 [pubmed]
PHST- 2014/02/26 06:00 [medline]
PHST- 2014/07/01 00:00 [pmc-release]
AID - iovs.13-11821 [pii]
AID - 10.1167/iovs.13-11821 [doi]
PST - epublish
SO  - Invest Ophthalmol Vis Sci. 2014 Jan 13;55(1):247-58. doi: 10.1167/iovs.13-11821.