October 2010




Sweet success: delving into diabetic cataracts

by Maxine Lipner Senior EyeWorld Contributing Editor


Reviewing the ins and outs of cataract formation in the diabetic population

Dense posterior subcapsular cataract in a severe diabetic with long-standing poor control of blood sugar Source: Warren Hill, M.D.

Diabetic patients tend to develop cataracts earlier and about 25% more frequently than non-diabetic subjects, according to Irina G. Obrosova, Ph.D., professor, Pennington Biomedical Research Center, Baton Rouge, La. Dr. Obrosova offered up findings on such cataracts from a complete literature search on diabetes and cataractogenesis in the March issue of Diabetic Metabolism Research and Reviews. There are several links between diabetic eyes and cataract development. "Several of the genetic mechanisms including sorbitol pathway activation, non-enzymatic ligation, and oxidative stress lead to cataract development," Dr. Obrosova said. Investigators found that all the mechanisms are activated by high glucose.

The hope was that by delving into the literature investigators could better elucidate the mechanism at play and that this could potentially lead to a treatment. "The reason for looking at the mechanisms is that the better one understands mechanisms underlying disease, the better the chance that good therapeutics can be developed," Dr. Obrosova said. "The main reason for looking at the biochemical mechanism is to develop pharmacologic agents as well as other approaches to target and inhibit those mechanisms."

The diabetic connection

Cataracts in the diabetic population can be unique. "Diabetic cataracts developing in patients with juvenile diabetes are morphologically different," Dr. Obrosova said. "Patients with juvenile diabetes develop bilateral snowflake-type cortical deposits and posterior subcapsular cataracts." For those with type 2 diabetes, the morphology is no different than for other cataract patients; however, it tends to develop sooner. "It develops earlier in subjects with diabetes compared with non-diabetic subjects," Dr. Obrosova said. These type 2 patients also develop opacities that are not present in the type I patients such as posterior subcapsular cataracts and nuclear opacities.

Keeping cataracts at bay in any diabetic patient requires a special approach. "The main treatment is to maintain good blood glucose control," Dr. Obrosova said. "The better the blood glucose control, the more effective the prevention of cataractogenesis will be." When it comes to cataract removal, however, there are no differences. "Cataract surgery remains the only option," Dr. Obrosova said. "Many approaches have been tested, like combinations of nutrients and combinations of antioxidants, but the results of those trials are inconclusive so we cannot say that these approaches effectively prevent or delay cataract."

Understanding the mechanisms

Some inroads have been made into the mechanisms contributing to cataractogenesis. One investigator, Peter F. Kador, Ph.D., Omaha, Neb., discovered the role of the sorbitol pathway. "He extensively characterized the effects of many aldose reductase inhibitors on cataract in different animal species," Dr. Obrosova said. "He was also the first to find that diabetic cataracts are completely prevented by aldose reductase inhibitors, which was confirmed later by many other authors."

Another author, Stephen S. Chung, Ph.D., University of Hong Kong, Hong Kong, developed key data on aldose reductase and cataracts. "He worked a lot with a transgenic mouse model and produced very elegant data in support of the role of aldose reductase from cataractogenesis," Dr. Obrosova said.

Dr. Obrosova has also developed some important findings on the diabetic cataract connection. "I worked a lot on biochemical changes in the diabetic lens and my group was the first to discover the role for poly [ADP-ribose] polymerase," Dr. Obrosova said. "This enzyme has also been implicated in cancer, cardiovascular diseases, neurodegenerative disease, and in some inflammation."

By delving into the mechanisms here, the hope is that new treatments can be derived. "We hope that better understanding of mechanisms will lead to the development of new therapeutic approaches to delay and prevent diabetic cataractogenesis," Dr. Obrosova said. Unfortunately, aldose reductase inhibitors have fallen short. "The problem is that aldose reductase inhibitors are very effective at preventing cataracts but they have been eliminated from any eye disease-related clinical trials because of adverse side effects," Dr. Obrosova said. "Maybe new classes of aldose reductase inhibitors will be developed in the future, but at present there are no clinical trials because previous ones were associated with problems."

Going forward, Dr. Obrosova hopes that new developments will soon be made. "Maybe new approaches for drug delivery into the eye would help," she said. "For example, if it would be possible to deliver aldose reductase inhibitor directly into the eye it may solve the problem of drug toxicity." Dr. Obrosova thinks that understanding of new genetic mechanisms and improvements in systems of drug delivery will make the difference. "Then effective agents for preventing cataracts in human subjects will be found," she said.

Editors' note: Dr. Obrosova has no financial interests related to her comments.

Contact information

Obrosova: 225-763-0276, obrosoig@pbrc.edu

Sweet success: delving into diabetic cataracts Sweet success: delving into diabetic cataracts
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