Abstract
Age-associated sterile inflammation can cause dysregulated choroidal neovascularization (CNV) as age-related macular degeneration (AMD). Intraocular fluid screening of 234 AMD patients identified high levels of IL-4. The purpose of this study was to determine the functional role of IL-4 in CNV formation using murine CNV model. Our results indicate that the IL-4/IL-4 receptors (IL4Rs) controlled tube formation and global proangiogenic responses of bone marrow cells. CCR2+ bone marrow cells were recruited to form very early CNV lesions. IL-4 rapidly induces CCL2, which enhances recruitment of CCR2+ bone marrow cells. This in vivo communication, like quorum-sensing, was followed by the induction of IL-4 by the bone marrow cells during the formation of mature CNVs. For CNV development, IL-4 in bone marrow cells are critically required, and IL-4 directly promotes CNV formation mainly by IL-4R. The IL-4/IL-4Rα axis contributes to pathological angiogenesis through communications with bone marrow cells leading to retinal degeneration.
Highlights
Age-related macular degeneration (AMD) is a neurodegenerative disorder which develops in elderly individuals and is a major cause of visual impairments in developed countries
The results showed that the AMD patients had significantly higher levels of IL-4 in their aqueous than in normal subjects (Table 1, Table 2)
We examined whether the IL-4 levels were significantly associated with the different subtypes of AMD
Summary
Age-related macular degeneration (AMD) is a neurodegenerative disorder which develops in elderly individuals and is a major cause of visual impairments in developed countries. In the early stages of AMD, lipoprotein deposits called drusen accumulate in the subretinal space between the photoreceptors and retinal pigment epithelium (RPE). Drusen are associated with the degeneration of the RPE which leads to a dysfunction or loss of the photoreceptors. Choroidal (CNVs) develop in the subretinal space, and the CNVs lead to degeneration of the photoreceptor cells, infiltration by inflammatory cells, activation of microglia, and ganglion cell loss (Beck et al, 2016; Copland et al, 2018). CCL2 plays an important role in recruiting bone marrow cells, monocytes, and macrophages to the ocular neovascularizations. In this disease process, the bone marrow plays an important role by supplying new vascular endothelial cells and macrophages to the retina (Gao et al, 2016; Zhou et al, 2017). The bone marrow plays a key role in the repair of damaged tissues
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