Inflammation and Pharmacological Treatment in Diabetic Retinopathy

Abstract

Diabetic retinopathy (DR), the most common microvascular complication of diabetes mellitus, is estimated to be the leading cause of new blindness in the working population of developed countries. Primary interventions such as intensive glycemic control, strict blood pressure regulation, and lipid-modifying therapy as well as local ocular treatment (laser photocoagulation and pars plana vitrectomy) can significantly reduce the risk of retinopathy occurrence and progression. Considering the limitations of current DR treatments development of new therapeutic strategies, it becomes necessary to focus on pharmacological treatment. Currently, there is increasing evidence that inflammatory processes have a considerable role in the pathogenesis of DR with multiple studies showing an association of various systemic as well as local (vitreous and aqueous fluid) inflammatory factors and the progression of DR. Since inflammation is identified as a relevant mechanism, significant effort has been directed to the development of new concepts for the prevention and treatment of DR acting on the inflammatory processes and the use of pharmacological agents with anti-inflammatory effect. Inhibiting the inflammatory pathway could be an appealing treatment option for DR in future practices, and as further prospective randomized clinical trials accumulate data, the role and guidelines of anti-inflammatory pharmacologic treatments will become clearer.

Nuclear receptor RORα regulates pathologic retinal angiogenesis by modulating SOCS3-dependent inflammation

“…This notion is consistent with minimal RORα staining in lectin positive retinal blood vessels ( (21). Increased levels of proinflammatory cytokines were found in vitreous fluid of patients with proliferative retinopathy (22). We next evaluated whether RORα controls pathologic retinal neovascularization through modulation of retinal inflammation.…”

Fenofibrate Exerts Protective Effects in Diabetic Retinopathy via Inhibition of the ANGPTL3 Pathway

“…P53 and Bax play crucial roles in apoptosis, which are in turn critical in pathogenesis in diabetic retinopathy. 11,12 As shown in Figure 2, our results suggested that the protein ( Fig. 2A) and mRNA (Fig.…”

Mechanistic Insights into Pathological Changes in the Diabetic Retina

“…62 Nonsteroidal anti-inflammatory drugs are a class of drugs that elicit anti-inflammatory effects by inhibiting cyclooxygenase enzyme-mediated prostaglandin formation. 63,64 At high doses, cyclooxygenase-2 inhibitor meloxicam has been shown to reduce endothelial NO synthase concentrations, 62 NF-kB activation levels, 37 and leukocyte adhesion 62 in diabetic retinas. In addition, our study indicates that fenofibrate can reduce high glucose-induced cyclooxygenase-2 up-regulation to exhibit anti-inflammatory effects.…”

“…In addition, our study indicates that fenofibrate can reduce high glucose-induced cyclooxygenase-2 up-regulation to exhibit anti-inflammatory effects. 65 Aspirin has also been shown to significantly reduce the adhesiveness of leukocytes 62 and, at high doses, to minimize the development of microvascular lesions in patients in non-proliferative DR. 64,66,67 Leukocytes have been shown to play a major role in the degeneration of retinal capillaries in DR. 33,34 Leukocyte integrin a m b 2 (alias CD11b/CD18 or MAC1), a protein mediating adhesion between leukocytes and endothelial cells, has been shown to facilitate such damage to endothelial cells by activating leukocytes. 33 Diabetes causes a significant increase in leukocyte adhesion to the retinal microvasculature (leukostasis), and selective antagonism of that adhesion by expression of neutrophil inhibitory factor has been shown to inhibit the diabetes-induced degeneration of retinal capillaries.…”