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.

Effects of Gold Nanoparticles Phytoreduced with Rutin in an Early Rat Model of Diabetic Retinopathy and Cataracts

“…Thus, VEGF-related mechanisms may be characteristic for more advanced DR. This supposition is further supported by Shi et al and Xiao et al, who found that retinal vessel permeability was significantly increased only after the eighth week of diabetes [55,56]. Furthermore, upon histopathological examination of the retina, a characteristic of early DR was noticed, neural degeneration [57].…”

Network pharmacology mechanism of Scutellarin to inhibit RGC pyroptosis in diabetic retinopathy

“…For TNF-α, study indicated that the expression of TNF-α mRNA was significantly increased in diabetic rats induced by a single intraperitoneal injection of 60 mg/kg STZ, and Adeno-associated virus (AAV)-mediated expression of human TNF-α in the murine eye induces retinal inflammation 54 . More importantly, TNF-α released from the activated microglia induced BRB damage, which in turn leaded to inflammation of the retinal 55 .…”

Omega-3 Polyunsaturated Fatty Acids and Their Anti-Oxidant, Anti-Inflammatory and Neuroprotective Effects in Diabetic Retinopathy: A Narrative Review

“…While BCVA did improve with the use of ranibizumab, addition of DHA to these regimens led to an increase in the total antioxidant capacity (TAC) and to a larger reduction in the level of inflammatory cytokines, particularly IL-6. The reduction in IL-6 level is notable because there is evidence that pathways mediated by this cytokine are linked to vascular degenerative changes within the retina of patients with DR [44]. Furthermore, in terms of the clinical outcomes, a greater improvement of membrane thickness in patients with macular edema was observed with supplementary use of DHA-containing nutraceutical supplements, in addition to ranibizumab [43].…”