Abstract
Purpose: :
Age-related macular degeneration (AMD) is the most common cause of blindness in the western world. Histopathologic and genetic studies have shown that the complement system plays an important role in the progression of this disease. C5a and C3a are bioactive fragments of complement components C5 and C3, which may be capable of binding to and activating endothelial cells.
Methods: :
RNA isolated from human RPE/choroid and cultured human choroidal endothelial cells was assayed for the presence of C3aR and C5aR using isoform-specific RT-PCR. Human tissue sections of retina, RPE, and choroid were immunolabeled with antibodies directed against C3aR and C5aR. Multiple punches of human choroid from two different donor eyes were incubated for 24 hours in the presence of 1 µg/mL recombinant human C5a protein or the control protein, bovine serum albumin (BSA). Punches were immunolabeled with an anti-ICAM-1 antibody. Choriocapillary ICAM-1 labeling intensities were measured and compared.
Results: :
C5aR, but not C3aR, is present in human choroid in vivo, demonstrated by RT-PCR as well as immunohistochemistry. By immunohistochemistry, C5aR is present in the choriocapillaris. There was a 12% increase in ICAM-1 intensity (p-value < 0.001) in capillaries of choroid punches incubated with C5a protein in comparison to those incubated with BSA.
Conclusions: :
Choroidal endothelial cells express C5aR, and therefore the bioactive fragment C5a is able to bind to and possibly activate these cells. If C5a causes an increase of ICAM-1 on the surface of endothelial cells in the macula, it may be responsible for a local increase of leukocyte infiltration. Complement component C5a may therefore play a role in AMD pathogenesis progression through the activation of increased ICAM-1 production by choroidal endothelial cells.
Keywords: age-related macular degeneration • choroid • inflammation