Natural Immunity and Ocular Inflammation

We have focused on the role of innate immunity during the formation oföchoroidal neovascularization (CNV) -related diseasesù. Inflammation affects the formation and the progression of various vitreoretinal diseases. We performed a comprehensive analysis of inflammatory immune mediators in the vitreous fluids with diabetic macular edema, proliferative diabetic retinopathy, branch retinal vein occlusion, central retinal vein occlusion and rhegmatogenous retinal detachment. The concentrations of 20 soluble factors (nine cytokines, six chemokines, and five growth factors) were measured simultaneously by multiplex bead analysis system. Out of 20 soluble factors, three factors : interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1) were significantly elevated in all groups of vitreoretinal diseases compared with control group. According to the correlation analysis in the individual patientʼs level, these three factors that were simultaneously increased, did not show any independent upregulation in all the examined diseases. We also elucidated the role of natural killer (NK)T cells, which restricted CD1 molecule and participate in the innate immune response, in laser-induced experimental CNV. We examined CNV formation in independent two NKT cell-deficient mice, either CD1 knockout (KO) mice or Ja18 KO mice, and found that both KO mice showed significant reduction of experimental CNV. During the clinical process of CNV-related diseases, not only CNV formation, subretinal scaring is thought to be another important step. We thus established the experimental model of subretinal scaring by injecting peritoneal exudating macrophages into subretinal space. Subretinal fibrous tissue was observed by fundus scope in PEC-inoculated mice after seven days. The tissue was consisted of monotonous and low cell-density area, which expressed a-SMA with collagen synthesis. Because PEC-inoculated MCP-1 KO mice showed less amount of glial residual, not only exogenous macrophages, but also intrinsic macrophages are critical. Activated macrophages directly induced myofibrotic changes in RPE cells in vitro.