Diabetic Retinopathy: From Pathogenesis to Treatment

In spite of all advances in the understanding of chronic diabetic complications, diabetic retinopathy remains a significant clinical problem. The pathogenetic mechanisms leading to the development of diabetic retinopathy is indeed complex. Multiple interactive mechanisms may come into play leading to cellular damage and adaptive changes leading to the development of this devastating complication of diabetes. In this focused issue of the journal we have assembled several invited reviews, from well-recognized experts in their fields, as well as original research articles. These reviews provide state-of-the-art knowledge dealing with several mechanisms , all of which contribute to the development of diabetic retinopathy. The reviews include discussion on several pathogenetic mechanisms such as polyol pathway, oxida-tive stress, cellular signaling, inflammatory changes, and ex-citatory amino acids as well as pharmacotherapy in diabetic retinopathy. In addition, several excellent original research articles demonstrate novel pathophysologic aspects of this disease process which ranges from population-based studies to mechanistic studies. It is becoming more and more evident that early diabetic retinopathy is associated with increased production of several inflammatory mediators. Several pharmacological approaches by inhibiting production of inflammatory mediators are effective in preventing early lesions of diabetic retinopathy. Although this concept is relatively new, it has enormous potential as a drug target. Dr. T. S. Kern has discussed the inflammatory process in the pathogenesis of early stages of diabetic retinopathy. Dr. M. Lorenzi has reviewed polyol pathway activation as a mechanism for diabetic retinopathy. Interest in this pathway stems from the fact that it remains one of the attractive mechanisms to explain several cellular changes in hyper-glycemia. With new knowledge of this pathway and availability of novel aldose reduction inhibitors we will probably see new clinical trials in the near future. Inflammation or other changes like augmented polyol pathway activity leads to oxidative stress in the retina which disrupts the fine balance between formation and elimination of reactive oxygen species. Drs. Kowluru and Chan have emphasized that several metabolic abnormalities which are implicated in diabetic retinopathy are influenced by oxidative stress. Although currently little clinical data is available as to the effectiveness of blocking such pathways for the treatment of diabetic retinopathy, antioxidant treatment remains an attractive future option for pharmacotherapy for diabetic retinopathy. In an accompanied research article this group has also demonstrated that peroxinitrite accumulation and impaired scavenging of mitochondrial superoxide may be an important mechanism in the pathogenesis of retinopathy. In a research article, …