Sequential and Dynamic Variations of IL-6, CD18, ICAM, TNF-α, and Microstructure in the Early Stage of Diabetic Retinopathy

Abstract

Objective. The purpose of this project is to make sequential and indepth observation of the variations of retinal microvascular, microstructure, and inflammatory mediators at the early stage of diabetic retinopathy (DR) in streptozotocin-induced diabetes mellitus (DM) rats. Methods. DM was induced by a single intraperitoneal injection of 60 mg/kg body weight streptozotocin (STZ). The fluorescein fundus angiography, hematoxylin and eosin staining, periodic acid-Schiff staining, fluorescence imaging techniques, quantitative real-time PCR, and vascular endothelial growth factor- (VEGF-) A ELISA were performed on the 8th day, at the 4th week, 6th week, 8th week, and 10th week after DM induction, respectively. Results. In this study, we observed not only the decrease of retinal ganglion cells (RGCs) and the increase of endotheliocytes to pericytes (E/P) ratio, acellular capillaries, and type IV collagen-positive strands began to occur on the 8th day after induction but the vascular permeability and new vessel buds began to appear in the diabetes group at the 8th week, while the expression of VEGF-A, VEGF mRNA, IL-6 mRNA, ICAM mRNA, and TNF-α mRNA were significantly higher in the diabetes group compared with the normal group( $P<0.01$ ) on the 8th day after induction and maintained a high expression level throughout the 10-week observation period. However, the expression of CD18 mRNA began to increase significantly at the 4th week after induction and reached a peak at the 6th week. Conclusion. Our study indicated the abnormal alterations of microvessels, microstructure, and inflammatory mediators at the early stage of DR, which confirms and supplements the previous research, and also promotes an indepth understanding and exploration of the pathophysiology and underlying pathogenesis of DR.