Abstract
Age-related macular degeneration (AMD) is genetically associated with complement. Dendritic cells (DCs) play key roles during innate and adaptive immunity, and express complement components and their receptors. We investigated ocular DC heterogeneity and the role of DCs in the laser-induced choroidal neovascularization (CNV) model. In order to determine the function of DCs, we used two models of DC deficiency: the Flt3−/− and Flt3l−/− mouse. We identified three types of ocular DCs: plasmacytoid DC, classical DC-1, and classical DC-2. At steady-state, classical DCs were found in the iris and choroid but were not detectable in the retina. Plasmacytoid DCs existed at very low levels in iris, choroid, and retina. After laser injury, the number of each DC subset was up-regulated in the choroid and retina. In Flt3−/− mice, we found reduced numbers of classical DCs at steady-state, but each DC subset equally increased after laser injury between wildtype and Flt3−/− mice. In Flt3l−/− mice, each DC subsets was severely reduced after laser injury. Neither Flt3−/− or Flt3l−/− mice demonstrated reduced CNV area compared to wildtype mice. DCs do not play any significant role during the laser-induced CNV model of neovascular AMD.
Highlights
Age-related macular degeneration (AMD) is genetically associated with complement
We found that plasmacytoid Dendritic cells (DCs), cDC-1, and cDC-2 subtypes were detected in the mouse choroid, and all 3 subsets were increased during the laser-induced choroidal neovascularization (CNV) model
We show that DC heterogeneity exists in the eye, where we were able to detect classical DCs in the uvea, including the choroid and iris, but not in the retina (Fig. 2)
Summary
Dendritic cells (DCs) play key roles during innate and adaptive immunity, and express complement components and their receptors. We investigated ocular DC heterogeneity and the role of DCs in the laser-induced choroidal neovascularization (CNV) model. In Flt3−/− mice, we found reduced numbers of classical DCs at steady-state, but each DC subset increased after laser injury between wildtype and Flt3−/− mice. DCs do not play any significant role during the laserinduced CNV model of neovascular AMD. We found that plasmacytoid DCs, cDC-1, and cDC-2 subtypes were detected in the mouse choroid, and all 3 subsets were increased during the laser-induced CNV model. We found that DCs do not play a significant role during the laser-induced CNV mouse model of nAMD
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