gms | German Medical Science

Purpose: CNV in age-related macular degeneration (AMD) is thought to be an immunologically regulated process. Pioglitazone (PPARγ agonist) is an anti-diabetic drug with known anti-inflammatory properties. The aim was to investigate the anti-inflammatory and immune modulatory effects of Pioglitazone in a mouse model of laser-induced CNV.

Methods: Cultured and Pioglitazone-treated human retinal endothelial cells (hREC) were analysed by flow-cytometry (absolute cell numbers, proliferation and dead cells). CX3CR1+/GFP mice were fed either with Piogliazone or its vehicle cellulose and treated with an argon laser. Three and 14 days later, eyes were enucleated and retina and choroid separated. One day before, in vivo high resolution autofluorescence imaging for GFP-positive cells was performed. CX3CR1- and CD11b-positive cells were analysed by flow-cytometry. Pro- and anti-inflammatory cytokine expression (TNF-α , IL-6, IL-10) was evaluated by real-time PCR.

Results: In vitro, Pioglitazone did not show an effect on the proliferation of hREC. In vivo, a trend towards a reduction in the absolute numbers of CX3CR1- and CD11b-positive cells could be seen in the Pioglitazone group. A strong anti-inflammatory effect could be seen on cytokine levels. TNF-α and IL-6 were reduced and the anti-inflammatory IL-10 was upregulated. In autofluorescence imaging, markedly less GFP-positive cells were present in the area of the laser spots under Pioglitazone treatment.

Conclusion: Pioglitazone showed a strong anti-inflammatory effect on cytokine level and reduced the immigration of GFP-positive immune cells into the area of laser. Absolute immune cell numbers did not diminish significantly. Pioglitazone administration could be a therapeutic approach with an early influence in the cascade of CNV pathogenesis.