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From: Complement, Age-Related Macular Degeneration and a Vision of the Future
Arch Ophthalmol. 2010;128(3):349-358. doi:10.1001/archophthalmol.2010.18
Figure Legend:
Immunolocalization of complement factor H (CFH) and the membrane attack complex (MAC)/C5b-9 in the retinal pigment epithelium
(RPE)/choroid (Chor) complex. A and B, Confocal immunofluorescence images from an 84-year-old man with atrophic age-related
macular degeneration (AMD). Anti-CFH antibody labels substructural elements (arrows) in drusen (Dr) and the sub-RPE space
(green; Cy2 channel). C and D, Localization of CFH in drusen and the sub-RPE space in an 83-year-old man with AMD (green).
Drusen immunoreactivity (IR) is homogeneous; Copyright
CFH IR is©associated
with Medical
the choriocapillaris and the sub-RPE space (arrowheads).
2010 American
Date
of download:
8/3/2017
E-L, The
brown pigment
in the RPE cytoplasm andAssociation.
Chor is melanin.
E,
Localization
of CFH in drusen of a 79-year-old donor eye.
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Anti-CFH labeling (purple reaction product) is apparent in Dr, along the Bruch membrane (BM), and on the choroidal capillary walls
From: Complement, Age-Related Macular Degeneration and a Vision of the Future
Arch Ophthalmol. 2010;128(3):349-358. doi:10.1001/archophthalmol.2010.18
Figure Legend:
Confocal microscopic localization of the membrane attack complex (C5b-9) in drusen (Dr) and in compromised retinal pigment
epithelium (RPE) cells. A, Anti-C5b-9 labeling pattern at low magnification. Labeling in the choroid (Chor) (blue channel) is
unremarkable except for staining in the Bruch membrane (BM) and around the choriocapillaris. Two RPE cells that may be the
targets of complement attack are labeled (arrows). A nucleic acid-binding dye (YO-PRO; Invitrogen, Carlsbad, California) that also
binds to the elastic layer of BM is used to visualize
cell bodies
onAmerican
the green
channel. No nucleic acid staining is evident in the antiCopyright
© 2010
Medical
Date
of download:
8/3/2017
C5b-9–labeled
RPE
cells. B, Anti-C5b-9 labeling ofAssociation.
Dr (blue channel).
A
condensed
clump of lipofuscin granules (arrow) may have
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been expelled from the adjacent RPE cell. C, High magnification of a cell on the BM with anti-C5b-9 immunoreactivity on the basal
From: Complement, Age-Related Macular Degeneration and a Vision of the Future
Arch Ophthalmol. 2010;128(3):349-358. doi:10.1001/archophthalmol.2010.18
Figure Legend:
The complement system is composed of proteins that are activated through a cascade of enzymatic cleavage. Precursor proteins
are depicted in green, enzymes in red, byproducts in purple, and inactivated proteins in gray; red arrows indicate enzymatic
reactions. Complement factor H (CFH) plays a key regulatory role by inhibiting the binding of complement component 3b (C3b) to
complement factor B (CFB), thus preventing the formation of the alternative pathway's amplification loop C3 convertase (C3bBb) as
well as acting as a cofactor for the complement Copyright
factor I (CFI)–mediated
degradation
of the same convertase to inactive components
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Medical
Date
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iC3b of
and
Bb. MAC8/3/2017
indicates membrane attack complex;
MBL,
mannose-binding
lectin.
Association. All rights reserved.
From: Complement, Age-Related Macular Degeneration and a Vision of the Future
Arch Ophthalmol. 2010;128(3):349-358. doi:10.1001/archophthalmol.2010.18
Figure Legend:
A number of strategies for modulating the complement system are being considered for use in the treatment of various stages of
age-related macular degeneration. These include, in general, approaches to (1) inhibit activation and the assembly of convertases,
(2) promote the decay and proteolysis of macromolecular complexes, including the convertases, (3) block various effector
molecules, such as C3a and C5a, and (4) reestablish control and homeostasis of the system, such as augmentation with protective
complement factor H (CFH). This figure is a modified
version
of Figure
3; itMedical
depicts 4 potential targets within the complement
Copyright
© 2010
American
Date
of download:
8/3/2017
pathway
that are being
considered for therapeutic Association.
intervention:AllC1-INH,
which
rights reserved.inhibits activation of the classical pathway;
compstatin, which inhibits the activation of C3; sCR1, which promotes the degradation of the C3 convertase C3bBb; and