Immune response has been divided into innate immunity and acquired immunity. We focused on the role of innate immunity during the formation of uveitis and choroidal neovascularization (CNV)-related diseases. To carry out a comprehensive analysis of ocular inflammatory responses in patients with uveitis, vitreous fluid was analyzed using a microbead-based multiplex ELIZA system. We found that cytokines which were related with innate immunity were elevated, but cytokines which were related with acquired immunity were not. We also found that the role of IL-17 was to produce Th17 cells in the chronic phase of experimental uveitis. Next, we investigated the role of the natural killer (NK) T cells which restrict CD1 and participate in the innate immune response in laser-induced experimental CNV. We studied the CNV formation in two independent NK T cell-deficient strains of mice, CD1 knockout (KO) mice and Jalpha18 KO mice, and found that both KO mice showed significant reduction of the effects of experimental CNV. After laser treatment, both CD1 KO mice and Jalpha18 KO mice showed a decrease in the expression of vascular endothelial growth factor (VEGF) expression in retina and choroid. Interestingly, intravitreous inoculation of a galactosylceramide (alphaGalCer), which is the ligand of NK Tcells, inhibited CNV in C57BL6 mice. Collectively, we conclude that NK T cells play an important role in forming CNV as one of the inducers of VEGS. Because NK T cells bear the potential to regulate immune response, alphaGalCer might activate NK T cells differently to produce angiostatic factors and have a therapeutic potential in vivo. During the clinical process of CNV-related diseases, not only CNV formation, but also subretinal scarring is thought to be another important step. We thus established the experimental model of subretinal scaring by injecting peritoneal exudating macrophases into the subretinal space. This scaring was inhibited by inoculation of anti-IL-6 antibody and micro bubbles into the vitreous cavity following low power ultrasound treatment through the cornea.
|Pages (from-to)||279-297; discussion 298|
|Journal||Nippon Ganka Gakkai zasshi|
|Publication status||Published - Mar 2008|
All Science Journal Classification (ASJC) codes