Role of endocannabinoids in the progression of diabetic retinopathy

Abstract

In the past decades, the role of numerous factors in the pathophysiology of diabetic retinopathy has been explored, following which marked progress has been made in developing several novel therapeutic options, such as anti-vascular endothelial growth factor, anti-tumor necrosis factor-alpha and various other anti-inflammatory and anti-angiogenic agents, for the treatment of diabetic retinopathy. However, the involvement of endocannabinoid system in its pathogenesis has not been much explored. This review aims at unveiling every aspect of association of the endocannabinoid system and its interactions with various physiological and pathological pathways to induce disease progression. The various alterations induced by endocannabinoids, such as anandamide and 2-arachidonylglycerol, in retina during hyperglycaemia clearly demonstrate and verify their involvement in aggravating the pathological conditions, hence leading to the progression of diabetic retinopathy. Exploring this involvement furthermore, in greater depths, might be beneficial in acknowledging and understanding the hidden aspects of the pathogenesis of this complication even better and might provide a therapeutically beneficial alternative target to combat and restrict its progression amongst diabetic patients.

The Role of Inflammation in Retinal Neurodegeneration and Degenerative Diseases

“…Norgestrel can inhibit apoptosis and inflammation through the regulation of progesterone receptor membrane component 1 [ 149 ]. Another target for the treatment of retinal degeneration diseases is the use of endocannabinoid system receptor agonists (CB1 and CB2), which have a neuroprotective role and anti-inflammatory properties in neurogenerative diseases [ 150 ].…”

Lipopolysaccharide-Induced Functional Alteration of P-glycoprotein in the Ex Vivo Rat Inner Blood–Retinal Barrier

“…Furthermore, it was suggested that this effect of LPS on the P-gp activity is mediated by signaling via TLR4, TNF-α, TNF-R1, ET-1, ET B receptor, NOS, and PKC. As endogenous P-gp substrates related to the pathogenesis of DR [ 15 ], endocannabinoids such as anandamide are known through inducing expression of various inflammatory mediators [ 16 ]. It is considered that a functional decrease in P-gp at the inner BRB increases the retinal concentration of P-gp substrates including endocannabinoids.…”

“…Since the inflammation which is induced by the elevated LPS levels is considered to be involved in the progression of diabetic retinopathy (DR), a serious retinal disease [ 14 ], mechanisms of LPS-related DR pathogenesis should be understood. It has been reported that P-gp accepts endogenous compounds which are involved in the pathogenesis of DR [ 15 , 16 ]. Hence, it is hypothesized that P-gp at the inner BRB is affected by increased LPS concentration in the circulating blood of diabetic patients and thus takes part in the onset and/or development of DR.…”

Distinctive Evidence Involved in the Role of Endocannabinoid Signalling in Parkinson’s Disease: A Perspective on Associated Therapeutic Interventions

“…The ECS is a biological lipid-transmitting cascade that includes eCBs, molecules derived from arachidonic acid, and membrane phospholipids. The activity of CBs is expressed via Gi/o protein-coupled receptors, the CB1 receptor, and the cannabinoid 2 (CB2) receptor, being mediated via binding of the ligands to the metabotropic receptor; as well, other receptors are mentioned below, along with the enzymes and agents responsible for the synthesis, degradation, and transportation of eCB, which are essential elements of the body in both physiological and pathological aspects [ 30 , 31 , 32 ]. The detailed understanding of cannabinoid receptors, their specific locations and actions in the brain was followed by isolation of 2-endogenous arachidonic acid-derived ligands, anandamide/arachidonoyl ethanol amide (AEA), and 2-arachidonoyl glycerol (2-AG), the best-identified eCBs where the former was first to be isolated from porcine brain, and the latter obtained from canine intestines [ 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ].…”