Involvement of innate immunity in the course of choroidal neovascularization in mice

AbstractPurposeTo investigate the effect of retinal microglia depletion, and the effect of systemic lipopolysaccharide (LPS) exposure, in the course of laser‐induced choroidal neovascularization (CNV) in mice.MethodsFor microglia depletion, C57BL6/J mice were kept under a diet containing the colony‐stimulating factor 1 receptor (CSF‐1R) inhibitor PLX5622, for 1 week prior to CNV induction and until the end of the experiments. To evaluate the effect of systemic LPS challenge on the CNV course, LPS (1 mg/kg) was given intravenously in control‐fed mice for 1 or 4 consecutive days, immediately after CNV. Mice were imaged with optical coherence tomography (OCT) and fluorescein angiography (FA) at baseline, and at day 3, 7 and 14 after CNV. CNV lesions were measured in the FA images and flow cytometry was used to investigate the effects of PLX5622 on the innate immune cell populations in the retina and the choroid‐RPE of CNV‐subjected mice.ResultsPLX5622 led to microglia depletion in the retina, reduced numbers of dendritic cells, macrophages and leukocytes in the choroid‐RPE and a faster involution of CNV. Retinal swelling, vasodilation and accumulation of microglia/macrophages around retinal vessels were observed at day 4 after the first LPS challenge but not 1 day after a single LPS injection. Moreover, a single LPS injection led to exacerbation of the CNV lesion, while 4 consecutive LPS injections did not affect the CNV size compared to non‐injected mice.ConclusionsThe data suggest that suppression of the ocular innate immune response leads to a faster involution of CNV, while activation of innate immune cells with an acute systemic inflammatory stimulus results in increased CNV areas and slower involution. Moreover, chronic systemic LPS exposure do not affect the course of CNV. These findings highlight the importance of innate immunity in the course of experimental CNV and the different effects of acute and chronic systemic inflammation in the diseased retina.