The role of inflammation in immune system of diabetic retinopathy: Molecular mechanisms, pathogenetic role and therapeutic implications

Abstract

Diabetic retinopathy is one of the most common complications of diabetes mellitus and the leading cause of low vision and blindness worldwide. Mounting evidence demonstrates that inflammation is a key mechanism driving diabetes-associated retinal disturbance, yet the pathophysiological process and molecular mechanisms of inflammation underlying diabetic retinopathy are not fully understood. Cytokines, chemokines, and adhesion molecules interact with each other to form a complex molecular network that propagates the inflammatory and pathological cascade of diabetic retinopathy. Therefore, it is important to understand and elucidate inflammation-related mechanisms behind diabetic retinopathy progression. Here, we review the current understanding of the pathology and pathogenesis of inflammation in diabetic retinopathy. In addition, we also summarize the relevant clinical trials to further suggest inflammation-targeted therapeutics for prevention and management of diabetic retinopathy.

Alleviation of Diabetic Retinopathy by Glucose-Triggered Delivery of Vitamin D via Dextran-Gated Functionalized Mesoporous Silica Nanoparticles

“…Once the cytokines are activated, they help to release ICAM-1 and VCAM-1, which recruit monocytes and leucocytes to sustain ongoing inflammatory response. Chronic inflammation and inflammatory cells damage tissues, exacerbating retinal vascular penetrability, vasodilation, and retinal thickening in individuals with DR Figure demonstrates that the proinflammatory cytokine IL-6 was found to be increased in HG-treated ARPE-19 cells in comparison with the LG control group.…”

“…Chronic, low-grade inflammation is linked with vascular abnormalities observed in diabetic retinopathy . The level of inflammatory mediators including chemokines, like MCP-1 and cytokines, such as IL-6 and TNF-α, are considerably higher in DR . Once the cytokines are activated, they help to release ICAM-1 and VCAM-1, which recruit monocytes and leucocytes to sustain ongoing inflammatory response.…”

“…55 The level of inflammatory mediators including chemokines, like MCP-1 and cytokines, such as IL-6 and TNF-α, are considerably higher in DR. 56 Once the cytokines are activated, they help to release ICAM-1 and VCAM-1, which recruit monocytes and leucocytes to sustain ongoing inflammatory response. Chronic inflammation and inflammatory cells damage tissues, exacerbating retinal vascular penetrability, vasodilation, and retinal thickening in individuals with DR. 56 Figure 9 demonstrates that the proinflammatory cytokine IL-6 was found to be increased in HG-treated ARPE-19 cells in comparison with the LG control group. The current study examined whether MSN-CPBA-VD-Dex could prevent an HGinduced increase in the proinflammatory marker IL-6 in vitro.…”

Ultrasmall Coordination Polymer Nanodots Fe‐Quer Nanozymes for Preventing and Delaying the Development and Progression of Diabetic Retinopathy

“…On the one hand, ROS or oxidative stress can directly or indirectly trigger the release of inflammatory mediators and directly alter the expression of various inflammation‐related genes, thus participating in inflammatory processes that are closely related to the mechanism of DR pathogenesis. [ 24 ] In contrast, different peroxides and superoxides produced because of hyperglycemia contribute to the inflammatory response through various pathways. The resulting negative consequences include damage to vascular endothelial cells, an increase in microvascular permeability and the release of cytokines that promote neutrophil recruitment to the site of inflammation.…”

The U-Shape Relationship between Triglyceride-Glucose Index and the Risk of Diabetic Retinopathy among the US Population

“…In the past, the prevention and treatment of DR focused mainly on managing blood glucose levels and glycosylated hemoglobin levels in diabetic patients. Nevertheless, the pathogenesis of DR is a multifaceted process, and several mechanisms and factors contribute to its occurrence and progression, such as hypertension, abnormal lipid metabolism, inflammation and insulin resistance [ 2 , 3 , 4 ].…”