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Anne F. Alex, Sebastian Cordes, Peter Heiduschka, Nicole Eter; Effects of Pioglitazone on immune modulation in choroidal neovascularization. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2245.
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© ARVO (1962-2015); The Authors (2016-present)
Choroidal neovascularization (CNV) is pathognomic in the wet form of age-related macular degeneration (AMD) and can lead to retinal bleeding and severe vision loss. The latest hypothesis of pathogenesis is an immune cell regulated process of CNV. Pioglitazone (PPARγ agonist) is an anti-diabetic drug with known anti-inflammatory properties. The aim of this study was to investigate the anti-inflammatory and immune modulatory effects of pioglitazone in a mouse model of laser-induced CNV.
Human retinal endothelial cells (hREC) were incubated with different concentrations of pioglitazone. Absolute cell numbers, living and dead cells were determined and proliferation measured by flow cytometry. Furthermore, CX3CR1+/GFP mice were fed with either pioglitazone or its solvent cellulose and treated with an argon laser. Six and 14 days after laser, eyes were enucleated and retina and choroid separated. One day before, some mice were anaesthetized and autofluorescence imaging for GFP-positive cells was performed. For flow cytometric analysis, CD11b staining for determination of microglial cells was performed and cell characteristics measured. With real-time PCR, the changes of pro- and anti-inflammatory cytokine levels (TNFα, IL-6, IL-10) were evaluated.
In vitro, pioglitazone did not show an effect on the proliferation of hREC.In vivo, six days after laser, a strong trend in the reduction of GFP-positive cells could be measured in the pioglitazone treated group. CD11b high cells, representing microglia, were reduced. GFP-positive cells were hardly reduced 14 days after laser.A strong anti-inflammatory effect could be seen on cytokine levels. Both, TNFα and IL-6, were reduced in the pioglitazone treated group. The anti-inflammatory IL-10 was upregulated.In autofluorescence imaging, markedly less GFP-positive cell were present in the area of laser under pioglitazone treatment.
Pioglitazone showed a strong anti-inflammatory effect in laser-induced CNV. Repeatedly, a strong trend in the reduction of CX3CR1-positive immune cells could be demonstrated six days after laser. Additionally, the immigration of immune cells into the area of laser was obviously reduced in autofluorescence imaging.Pioglitazone could be a therapeutic approach, which interacts earlier in the cascade of CNV pathogenesis.
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