The critical role of ocular-infiltrating macrophages in the development of choroidal neovascularization

Abstract

Choroidal neovascularization (CNV) is directly related to visual loss in some eye diseases, such as age-related macular degeneration. Although several human histological studies have suggested the participation of macrophages in CNV formation, the precise mechanisms are still not fully understood. In this study, we elucidated the role of ocular-infiltrating macrophages in experimental CNV using CCR2 knockout (KO) mice, wild-type mice, and C57BL/6 (B6) mice. CCR2 is the receptor of monocyte chemoattractant protein-1, and the number of infiltrating macrophage and the area of CNV were significantly reduced in CCR2 KO mice. Enriched ocular-infiltrating macrophages from B6 mice actually showed angiogenic ability in a dorsal air sac assay. Moreover, their expression of class II, CD40, B7-1 and B7-2 molecules, and the mRNA for potential angiogenic factors, such as vascular endothelial growth factor, basic fibroblast growth factor, and tumor necrosis factor alpha, was also observed. Collectively, we conclude that ocular-infiltrating macrophages play an important role in CNV generation.

The Ratio of the Absolute Lymphocyte Count to the Absolute Monocyte Count Is Associated with Prognosis in Hodgkin's Lymphoma: Correlation with Tumor-Associated Macrophages

“…Peripheral monocytosis has been associated with a poor prognosis in patients with lymphomas as well as those with solid tumors [21][22][23]. Myeloid-lineage cells may promote tumorigenesis through immunosuppression and the promotion of the tumor vasculature required for tumor growth and progression [24,25]. TAMs are a source of vascular endothelial growth factor (VEGF)-A, promoting tumor angiogenesis [24,25].…”

“…Myeloid-lineage cells may promote tumorigenesis through immunosuppression and the promotion of the tumor vasculature required for tumor growth and progression [24,25]. TAMs are a source of vascular endothelial growth factor (VEGF)-A, promoting tumor angiogenesis [24,25]. TAMs also secrete matrix metalloproteinase 9, facilitating liberation of VEGF from the extracellular matrix [26,27].…”

Macrophages in neovascular age-related macular degeneration: friends or foes?

“…When Bruch's membrane of these animals is ruptured with thermal laser, they were found to produce much smaller neovascular membranes than wild-type mice. 67 Mice deficient for the endothelial surface molecule intercellular adhesion molecule-1 or one of its binding partners, CD18, also demonstrated impaired neovascularization following laser treatment. 68 Thus, both pharmacologic and genetic impairment of monocytes appear protective against CNV in several studies.…”

Expression of TNF-α and IL-6 cytokines in the choroid and sclera of hypercholesterolemic rabbits

“…Macrophages, retinal pigment epithelial (RPE) cells, and endothelial cells (EC) play an important role in the pathogenesis of ocular inflammation and the co nsequent formation of subretinal neovascular membrane (CNV). These cells secrete various inflammatory, growth, and angiogenic factors as well as pro-inflammatory cytokines, which contribute to the development of wet AMD (3)(4)(5) . The role of growth factors, such as vascular endothelial growth factor (VEGF), on the formation of CNV has been identified.…”