Abstract
Purpose :
Type-2 diabetics have an increased risk of macrovascular and microvascular complications including diabetic retinopathy. Hyperglycemia and inflammation are the major factors leading to severe diabetic adversitites. Ant-inflammatory and anti-diabetic medication may prevent disease progression. We investigated the impact of zinc complex of acetylsalicylic acid (Zn(ASA)2) on changes in retinal gene expression in Zucker diabetic fatty (ZDF) rats, an experimental model of type-2 diabetic retinopathy.
Methods :
At the age of 25 weeks, nondiabetic control (ZL) and obese ZDF rats were pretreated orally with vehicle or Zn(ASA)2 for 24 days. At the age of 29-30 weeks, RNA was extracted from retinas. Reverse transcription for the synthesis of cDNA was performed to determine the expression patterns of 84 selected genes involved in inflammation using micrfluidic card PCR technology (rt-PCR).
Results :
Treatement with Zn(ASA)2 significantly decreased plasma glucose concentration (39.6mM±3.1 vs 50.4mM±2.6, p<0.05). Plasma insullin levels remained similar among the groups. Compared to ZL rats, the retinal gene expression of inflammatory genes (BMP2, CCL2, CCL20, CCL3, CCL4, CCL7, CCR1, CCR3, CXCL10, CXCL6, CXCL9, FASLG, IL13, IL15, IL17A, IL17B, IL1B, IL33, IL4, TNF, VEGF-A and VFRSF11B) were at least two fold higher in ZDF rats. In contrast to the vehicle group, genes related to the inflammatory response (CCL2, CCL20, CCL3, CXCL6, IL13, IL17A and VEGF-A) were significantly decreased in obese ZDF rats.
Conclusions :
Zn(ASA)2 sustains glucose metabolism. Retinal inflammation has a severe impact on ZDF rats diabetic retinopathy. The anti-inflammatory effect of Zn(ASA)2 reversed changes in gene expression in diabetic retinopathy of ZDF rats.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.