diabetic retinopathy: from pathogenesis to...

Hindawi Publishing CorporationExperimental Diabetes ResearchVolume 2007, Article ID 69527, 2 pagesdoi:10.1155/2007/69527

EditorialDiabetic Retinopathy: From Pathogenesis to Treatment

Subrata Chakrabarti

Received 20 September 2007; Accepted 20 September 2007

Copyright © 2007 Subrata Chakrabarti. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.

In spite of all advances in the understanding of chronic di-abetic complications, diabetic retinopathy remains a signifi-cant clinical problem. The pathogenetic mechanisms leadingto the development of diabetic retinopathy is indeed com-plex. Multiple interactive mechanisms may come into playleading to cellular damage and adaptive changes leading tothe development of this devastating complication of diabetes.

In this focused issue of the journal we have assembledseveral invited reviews, from well-recognized experts in theirfields, as well as original research articles. These reviews pro-vide state-of-the-art knowledge dealing with several mech-anisms, all of which contribute to the development of di-abetic retinopathy. The reviews include discussion on sev-eral pathogenetic mechanisms such as polyol pathway, oxida-tive stress, cellular signaling, inflammatory changes, and ex-citatory amino acids as well as pharmacotherapy in diabeticretinopathy. In addition, several excellent original researcharticles demonstrate novel pathophysologic aspects of thisdisease process which ranges from population-based studiesto mechanistic studies.

It is becoming more and more evident that early di-abetic retinopathy is associated with increased productionof several inflammatory mediators. Several pharmacologicalapproaches by inhibiting production of inflammatory me-diators are effective in preventing early lesions of diabeticretinopathy. Although this concept is relatively new, it hasenormous potential as a drug target. Dr. T. S. Kern has dis-cussed the inflammatory process in the pathogenesis of earlystages of diabetic retinopathy.

Dr. M. Lorenzi has reviewed polyol pathway activation asa mechanism for diabetic retinopathy. Interest in this path-way stems from the fact that it remains one of the attrac-tive mechanisms to explain several cellular changes in hyper-glycemia. With new knowledge of this pathway and availabil-ity of novel aldose reduction inhibitors we will probably seenew clinical trials in the near future.

Inflammation or other changes like augmented polyolpathway activity leads to oxidative stress in the retina which

disrupts the fine balance between formation and eliminationof reactive oxygen species. Drs. Kowluru and Chan have em-phasized that several metabolic abnormalities which are im-plicated in diabetic retinopathy are influenced by oxidativestress. Although currently little clinical data is available asto the effectiveness of blocking such pathways for the treat-ment of diabetic retinopathy, antioxidant treatment remainsan attractive future option for pharmacotherapy for diabeticretinopathy. In an accompanied research article this grouphas also demonstrated that peroxinitrite accumulation andimpaired scavenging of mitochondrial superoxide may be animportant mechanism in the pathogenesis of retinopathy.

In a research article, Dr. Canning et al. demonstrated therole of advanced glycation end products (AGEs) and galectin3 with AGE binding properties in the blood retinal bar-rier breakdown and VEGF upregulation. This research reem-phases the importance of such mechanisms in the pathogen-esis of early changes in diabetic retinopathy.

Furthermore, Drs. Khan and Chakrabarti discussed aplethora of intracellular signaling mechanisms ranging fromsecond messengers, transcription factors to transcriptioncoactivators that are of importance in functional and struc-tural changes in the microvasculature in diabetic retinopathy.

Dr. Pulido et al. addressed the relationship between dia-betic retinopathy and elevated glutamate level. Such elevatedglutamate levels may have toxic effects. In an accompaniedresearch article this group also demonstrated a method fordetection of glutamate.

Dr. Ross et al. reported results of an interesting clinicalstudy from Alberta, Canada. They have demonstrated thatethnicity does play a role in the development of diabeticretinopathy although the risk factors are similar between var-ious populations.

Finally, Drs. Schwartz and Flynn discussed clinical ex-perience with various pharmacological treatments. As moredata is available, the role of such treatment will be clearer andmay provide new adjuvant treatment in addition to photoco-agulation and laser treatment of diabetic retinopathy.

2 Experimental Diabetes Research

These articles, hopefully, will provide better understand-ing of this process and bring forward new ideas with respectto the development of newer adjuvant treatment modalities.However, as evident from these articles as well as data in theliterature, the pathogenetic mechanisms involved in diabeticretinopathy are interactive and interdependent. Hence, effec-tive future treatment strategies may include multiple phar-macological agents, targeted simultaneously to block multi-ple pathways.

Obviously not all aspects of this field could be addressedin one issue and I extend my apologies to many contribu-tors of this field whose work has not been covered. I thank allthe authors who contributed to this issue and the reviewersfor the highly constructive and helpful comments. My sin-cere thanks to Dr. A. A. F. Sima for providing me with anopportunity to work as an editor of this issue. It has been mydistinct privilege to work with these excellent scientists.

Subrata Chakrabarti

AUTHOR CONTACT INFORMATION

Subrata Chakrabarti: London Health Science Centre,Department of Pathology, The University of Western Ontario,London, ON, Canada N6A 5A5;[email protected]

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