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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. All rights reserved. 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 All rights reserved. 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 © 2010 American Medical Date download: 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