Pathophysiology and management of diabetic retinopathy

Abstract

Diabetic retinopathy remains a major cause of worldwide preventable blindness. In this review, we evaluate the recent advances in understanding the molecular mechanisms of diabetic retinopathy, highlight the current management of diabetic retinopathy and new therapeutic approaches, and discuss the range of potential future therapeutic strategies in order to combat the disease. The microvasculature of the retina responds to hyperglycemia through a number of biochemical changes, including the activation of PKC, increased advanced glycation endproducts formation, polyol pathway and oxidative stress, and activation of the renin-angiotensin system. There is an accumulating body of evidence that inflammation and neurodegeneration play a prominent role in the pathogenesis of diabetic retinopathy. Strict metabolic control, tight blood pressure control, laser photocoagulation and vitrectomy remain the standard care for diabetic retinopathy. Emerging therapies include intravitreal triamcinolone or anti-VEGF agents, ruboxistaurin, renin-angiotensin system blockers, fenofibrate, islet cell transplantation, PPAR-g agonists and intravitreal hyaluronidase. However, more randomized, controlled clinical trials are required to clarify their role alone or in combination. Learning objectivesUpon completion of this activity, participants should be able to:• Identify factors that contribute to the development of diabetic retinopathy Medscape: Continuing Medical Education OnlineThis activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of MedscapeCME and Expert Reviews Ltd. MedscapeCME is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. MedscapeCME designates this educational activity for a maximum of 1.5 AMA PRA Category 1 Credits™. Physicians should only claim credit commensurate with the extent of their participation in the activity. All other clinicians completing this activity will be issued a certificate of participation. To participate in this journal CME activity: (1) review the learning objectives and author disclosures; (2) study the education content; (3) take the post-test and/or complete the evaluation at http://cme.medscape.com/CME/expertreviews; (4) view/print certificate. For reprint orders, please contact reprints@expert-reviews.comExpert Rev. Ophthalmol. 4(6), (2009) 628Review Abu El-Asrar, Al-Mezaine & Ola CME Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and remains one of the leading causes of blindness worldwide among adults aged 20-74 years. The two most important visual complications of DR are diabetic macular edema (DME) and proliferative DR (PDR). The prevalence of DR increases with the duration of diabetes, and nearly all people with Type 1 diabetes, and more than 60% of those with Type 2, have some retinopathy after 20 years. In the Wisconsin Epide...

Neurodegeneration and Neuroprotection in Diabetic Retinopathy

“…Several studies indicate that even intensive therapy to control blood glucose has some long-term effects on the risk of DR [18,19]. In addition to high glucose, the dysregulated levels of excitotoxic metabolites, such as glutamate, homocysteine, branched chain amino acids, nutrients, hormones and several other factors, have been found to be implicated in neurodegeneration early in DR [20,21]. …”

Modulation of diabetic retinopathy pathophysiology by natural medicines through PPAR‐γ‐related pharmacology

“…The underlying pathophysiological mechanisms associated with hyperglycaemic‐induced DR are through excessive formation of advanced glycation end products (AGEs) and production of excessive oxidative stress (Ciulla et al ., 2003; Abu El‐Asrar et al ., 2009). Moreover, these biochemical mechanisms lead to a cascade of events, such as promotion of apoptosis, inflammation and angiogenesis, which induce damage to diabetic retina, leading to DR (Ciulla et al ., 2003; Abu El‐Asrar et al ., 2009; Figure 1).…”

“…The accumulated AGEs products are detected in the retinal blood vessel wall, responsible for mediating the pathological angiogenesis and hyper‐permeability in retina. Several bodies of evidence suggest that the interaction between AGEs and their receptor activates nicotinamide adenine dinucleotide phosphate oxidase and enhances the formation of oxygen radicals, with subsequent activation and translocation of nuclear factor‐kappaB (NF‐κB), followed by release of pro‐inflammatory cytokines and growth factors (Abu El‐Asrar et al ., 2009). Moreover, AGEs enhance apoptosis in retinal pericytes, corneal endothelial cells, neuronal cells and renal mesangial cells through increased oxidative stress or via induced expression of pro‐apoptotic cytokines (Kasper et al ., 2000; Denis et al ., 2002; Kaji et al ., 2003).…”

Association of Tumor Necrosis Factor Α, Interleukin 6, and Interleukin 10 Promoter Polymorphism With Proliferative Diabetic Retinopathy in Type 2 Diabetic Subjects

“…1 Visual loss because of diabetes either develops from increased permeability of retinal vessels (diabetic macular edema) or by proliferation of new retinal vessels. It is estimated that DM affects 4% of the world's population, and retinopathy occurs in almost all type 1 and 75% of type 2 DM cases within 15 years of inception of DM.…”