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| Figure 2: Hypothetical model for therapeutic intervention in diabetic retinopathy via augmentation of GPR109A signaling. Hyperglycemia and dyslipidemia are major features of diabetes and are known to potentiate factors that contribute to the increased oxidative stress and inflammation characteristic of the disease. Of those factors, clinical and experimental studies show upregulated Nuclear Factor-Kappab (NF-kB) and reduced Peroxisome Proliferator-Activated Receptor-Gamma (PPAR-γ) activity to be crucial. Studies conducted using non-retinal cells and tissues show GPR109A to be effective at reversing and/or inhibiting these parameters upon its activation by specific agonists. Additionally, GPR109A may elicit other direct effects congruent with reduced inflammation and oxidative stress. In retina, GPR109A is expressed in cells critical to the regulation of tissue immunity and inflammation (e.g., Retinal Pigment Epithelial (RPE) and microglia) and similarly suppresses inflammation and oxidative stress when activated. Thus, therapies to augment this phenomenon in diabetic retina may prevent or delay the development and progression of retinopathy. |
