期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 9, 页码 -出版社
MDPI
DOI: 10.3390/ijms22094335
关键词
diabetic retinopathy; AhR; VAF347; retinal inflammation; capillary degeneration; IL-17A
资金
- VA [BX003403]
- NEI [RO1 EY030487, P30 EY011373]
- Ohio Lions Eye Research Foundation
- Cleveland Eye Bank Foundation
- Research to Prevent Blindness Foundation
The study examined the efficacy of an AhR agonist, VAF347, as a potential therapeutic for non-proliferative diabetic retinopathy. It was found that the AhR agonist significantly reduced leukostasis, oxidative stress, and inflammation in the retina of diabetic mice, and ameliorated retinal capillary degeneration. These findings suggest that VAF347 could be a potentially novel therapeutic for non-proliferative diabetic retinopathy.
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.
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