Inflammatory Mechanisms of Age-Related Macular Degeneration
Inflammatory Mechanisms of Age-Related Macular Degeneration
A number of inflammatory cytokines have been found to be elevated either systemically in the serum or locally in the ocular tissue or fluids of patients with AMD. As mentioned above, systemic levels IL-6, IL-18, and TNF-α correlated with CFH haplotypes in AMD patients. Furthermore, systemic IL-6 levels have been shown to correlate with the incidence and progression of AMD. IL-18 has recently been reported to play a protective role against development of CNV. However, results are conflicting as to whether IL-18 functions in antiangiogenic manner. As discussed below, IL-18 may also be involved in RPE atrophy.
IL-22 and IL-17A, cytokines produced by the Th17 subset of helper CD4 T cells, were found to be elevated in the serum of patients with exudative AMD. Two single nucleotide polymorphisms within the IL-17A gene were recently reported to be associated with AMD as well as higher levels of IL-17A secretion from PBMC stimulated ex vivo. Elevated IL-17A and IL-17RC levels were also detected in AMD lesions compared with normal macular tissues. In vitro, IL-22 induced apoptosis of primary human RPE cells, and IL-17A was shown to enhance production of inflammatory cytokines, including IL-6, IL-8, and CCL2, from ARPE-19 cells as well as induce angiogenesis in human choroidal endothelial cells.
Several studies have used multiplex protein screens to identify cytokines in ocular fluids of patient with neovascular AMD.Table 2 lists select cytokines with direct involvement in inflammatory cascades. Consistent with the systemic findings discussed above, IL-6, which has proangiogenic properties, has been found in higher concentrations in aqueous fluid of eye with neovascular AMD compared with controls. However, as with many observations from human samples, whether these cytokines are involved in the primary pathogenesis of AMD or are a result of the disease process remains to be determined.
Inflammatory Cytokines in AMD
A number of inflammatory cytokines have been found to be elevated either systemically in the serum or locally in the ocular tissue or fluids of patients with AMD. As mentioned above, systemic levels IL-6, IL-18, and TNF-α correlated with CFH haplotypes in AMD patients. Furthermore, systemic IL-6 levels have been shown to correlate with the incidence and progression of AMD. IL-18 has recently been reported to play a protective role against development of CNV. However, results are conflicting as to whether IL-18 functions in antiangiogenic manner. As discussed below, IL-18 may also be involved in RPE atrophy.
IL-22 and IL-17A, cytokines produced by the Th17 subset of helper CD4 T cells, were found to be elevated in the serum of patients with exudative AMD. Two single nucleotide polymorphisms within the IL-17A gene were recently reported to be associated with AMD as well as higher levels of IL-17A secretion from PBMC stimulated ex vivo. Elevated IL-17A and IL-17RC levels were also detected in AMD lesions compared with normal macular tissues. In vitro, IL-22 induced apoptosis of primary human RPE cells, and IL-17A was shown to enhance production of inflammatory cytokines, including IL-6, IL-8, and CCL2, from ARPE-19 cells as well as induce angiogenesis in human choroidal endothelial cells.
Several studies have used multiplex protein screens to identify cytokines in ocular fluids of patient with neovascular AMD.Table 2 lists select cytokines with direct involvement in inflammatory cascades. Consistent with the systemic findings discussed above, IL-6, which has proangiogenic properties, has been found in higher concentrations in aqueous fluid of eye with neovascular AMD compared with controls. However, as with many observations from human samples, whether these cytokines are involved in the primary pathogenesis of AMD or are a result of the disease process remains to be determined.
