Neuroinflammation and neurodegeneration in diabetic retinopathy

Abstract

Diabetic retinopathy (DR) is the most common complication of diabetes and has been historically regarded as a microangiopathic disease. Now, the paradigm is shifting toward a more comprehensive view of diabetic retinal disease (DRD) as a tissue-specific neurovascular complication, in which persistently high glycemia causes not only microvascular damage and ischemia but also intraretinal inflammation and neuronal degeneration. Despite the increasing knowledge on the pathogenic pathways involved in DR, currently approved treatments are focused only on its late-stage vasculopathic complications, and a single molecular target, vascular endothelial growth factor (VEGF), has been extensively studied, leading to drug development and approval. In this review, we discuss the state of the art of research on neuroinflammation and neurodegeneration in diabetes, with a focus on pathophysiological studies on human subjects, in vivo imaging biomarkers, and clinical trials on novel therapeutic options.

Improvement of Inflammation and Abnormal Vascularization by TSP1 Treatment Combined with ADSCs Transplantation in Mice with Induced Polycystic Ovary Syndrome

“…[ 22 ] ITGAM can also respond to inflammation, and monocytes expressing ITGAM can secrete VEGF in the inflammatory area, thus promoting the formation of neovascularization. [ 54 ] When the inflammatory response and/or vascularization were inhibited by TSP1/ADSCs treatment, the expression level of ITGAM also decreased (Figure 5), suggesting its potential importance.…”

Inhibition of Galectins and the P2X7 Purinergic Receptor as a Therapeutic Approach in the Neurovascular Inflammation of Diabetic Retinopathy

“…Currently, intraretinal inflammation and neurodegeneration have emerged as key processes in DR progression [16,28]. Indeed, along with microvascular damage, inflammatory and neurodegenerative processes contribute to alterations in the "retinal neurovascular unit", a functional unit composed of endothelial cells, glial cells and neurons [29].…”

“…The "retinal neurovascular unit" includes specific retinal glia elements, such as microglial cells and macroglia (Müller cells and astrocytes) [28,33,34]. These express marked ERS [35][36][37] and subsequent activation of NLRP3 inflammasome [38], as a consequence of advanced glycation end products (AGEs) and reactive oxygen species (ROS) formation, strongly induced by chronic hyperglycemia [39].…”

Relationship between Biochemical Pathways and Non-Coding RNAs Involved in the Progression of Diabetic Retinopathy

“…The exact mechanism responsible for the development and progression of diabetic retinopathy is not fully understood, but extensive research has shed light on several key molecular processes involved. Moreover, DR has long been considered a microvascular complication of diabetes; however, growing evidence suggests that neurodegeneration is an early event in its pathogenesis [ 5 , 6 ]. DR is a common and debilitating microvascular complication of both type 1 and type 2 diabetes.…”