Aryl Hydrocarbon Receptor Agonist VAF347 Impedes Retinal Pathogenesis in Diabetic Mice

International Journal of Molecular Sciences

PatriciaR. Taylor¹  ThomasE. Zapadka¹  ChiehA. Lee¹  SarahI. Lindstrom¹  ScottJ. Howell¹  JuliaC. Batoki¹  BrooklynE. Taylor¹ 

[1] Department of Ophthalmology and Visual Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA;

关键词: diabetic retinopathy;    AhR;    VAF347;    retinal inflammation;    capillary degeneration;    IL-17A;   

DOI  :  10.3390/ijms22094335

来源: DOAJ

【 摘 要 】

Diabetic retinopathy is the leading cause of blindness in the working-age population worldwide. Although the cause of diabetic retinopathy is multifactorial, IL-17A is a prevalent inflammatory cytokine involved in the promotion of diabetes-mediated retinal inflammation and the progression of diabetic retinopathy. The primary source of IL-17A is Th17 cells, which are T helper cells that have been differentiated by dendritic cells in a proinflammatory cytokine environment. Aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that can manipulate dendritic cell maturation, halt the production of IL-6 (a proinflammatory cytokine), and suppress Th17 cell differentiation. In the current study, we examined the efficacy of an AhR agonist, VAF347, as a potential therapeutic for the onset of non-proliferative diabetic retinopathy in streptozotocin (STZ)-induced diabetic C57BL/6 mice. We determined that diabetes-mediated leukostasis, oxidative stress, and inflammation in the retina of STZ-diabetic mice were all significantly lower when treated with the AhR agonist VAF347. Furthermore, when VAF347 was subcutaneously injected into STZ-diabetic mice, retinal capillary degeneration was ameliorated, which is the hallmark of non-proliferative diabetic retinopathy in this diabetes murine model. Collectively, these findings provide evidence that the AhR agonist VAF347 could be a potentially novel therapeutic for non-proliferative diabetic retinopathy.

【 授权许可】

Unknown