Increased Prostaglandin E2 (PGE₂) Levels in Proliferative Diabetic Retinopathy, and Correlation with VEGF and Inflammatory Cytokines

Abstract

PGE(2) levels are significantly higher in the vitreous of patients with complications from proliferative diabetic retinopathy, and correlate with IP-10 and VEGF. The results of our study suggest that PGE(2) may have a pathogenic role in diabetic retinopathy and implicates a potential therapeutic role for nonsteroidal anti-inflammatory drugs. (ClinicalTrials.gov number, NCT01609881.).

Regulated in Development and DNA Damage 1 Is Necessary for Hyperglycemia-induced Vascular Endothelial Growth Factor Expression in the Retina of Diabetic Rodents

“…Expression of the proinflammatory marker tumor necrosis factor alpha (TNF-␣) is elevated in the vitreous of patients with DR (32,33) and Müller cell specific disruption of VEGF inhibits diabetes-induced overexpression of TNF-␣ (24). Since diabetes failed to enhance VEGF in the retina of REDD1 knock-out mice, we also evaluated TNF-␣ expression.…”

Reduction of Interleukin 8 and Platelet-Derived Growth Factor Levels by Topical Ketorolac, 0.45%, in Patients With Diabetic Retinopathy

“…3 In support of this, several studies have consistently shown elevated levels of inflammatory cytokines in the aqueous and vitreous of patients with proliferative DR (PDR) and diabetic macular edema. [4][5][6] Prostaglandins are an important class of inflammatory mediators that are biosynthesized from arachidonic acid by cyclooxygenase enzyme. 7 Nonsteroidal anti-inflammatory drugs (NSAIDs) are potent inhibitors of this enzyme and thereby the synthesis of all downstream prostaglandins.…”

“…9,10 Prostaglandins are elevated in animal models of DR, and progression of retinopathy can be prevented or delayed with prostaglandin inhibitors. [11][12][13][14] A recent pilot study reported elevated vitreous levels of prostaglandin E 2 (PGE 2 ) in patients with PDR, 4 and several prospective clinical studies have reported favorable effects on DR with systemic NSAIDs. [15][16][17][18] In 2009, ketorolac tromethamine, 0.45% (Acuvail; Allergan Inc), was approved for pain and inflammation after cataract surgery.…”

Proliferative Diabetic Retinopathy: An Overview of Vitreous Immune and Biomarkers

“…The most common interleukins found in DR patients are IL-6 and IL-8, where their concentrations were found increased in the vitreous of patients with PDR and prolonged hyperglycemia [3,42,47,[72][73][74][75][76][77][78][79][80][81][82]. Their role in the pathogenesis of PDR is still under investigation but evidence suggests the possibility of a rather direct contribution.…”