New discovery may hold hope for inflammatory eye disease treatment

Washington -- Researchers have discovered that uveitis, an inflammatory eye disease may be treated with a compound that blocks the action of aldose reductase, an enzyme essential to the production of inflammatory signaling molecules.

Uveitis, the inflammation of the uvea, a layer of tissue that lies just below the outer surface of the eyeball and includes the iris, is a condition that can be caused by both autoimmune and infectious diseases.

As yet, the only treatment that can be offered to reduced inflation is steroids, but these have serious side effects.

"The only thing a clinician can do now for uveitis is to treat the patient with steroids to reduce inflammation. But steroids have serious side effects, and you can‘t use them for a long period of time," assistant professor Kota Ramana of UTMB biochemistry and molecular biology and senior author of the study said.

Study‘s co -author Satish Srivastava, UTMB biochemistry and molecular biology professor, said that it‘s not much of a problem when uveitis is produced by an infection that can be killed off in a few days with antibiotics.

But if the source of the uveitis is an autoimmune disease like arthritis or lupus, in which the immune systemdefine mistakenly generates chronic inflammation in response to substances naturally present in the body, the lack of an alternative to steroids creates great difficulties for patients.

The researchers took a different route to reduce inflammation. They worked with rats that had been injected with a uveitis-generating bacterial toxin; and therefore demonstrated that the eye-damaging inflammation could be stopped by treatment with a compound that blocks the action of aldose reductase.

"We measured inflammatory markers in the untreated rats‘ eyes - during inflammation there are a lot of inflammatory signaling proteins and inflammatory cells secreted in the aqueous humor, the clear liquid inside the eyes," Ramana said.

"The concentrations of those proteins and cells are much lower when we used the aldose reductase inhibitor. When we also studied different sections of the eyes of rats treated with aldose reductase inhibitor, for example the retinal region, we saw the same reduction in the signaling molecules that cause damaging inflammation," he added.

The specific aldose reductase inhibitor used in the experiments was zopolrestat, which is currently in phase 3 clinical trials as a treatment for diabetic complications. But Srivastava said the same effect would likely be produced by other aldose reductase inhibitors, including one now approved for use in Japan.

"We have not reached the clinical trial stage as yet, but we are not far away. If the trials work out, we‘d like to go for topical administration in drops, which would mean that only the tissues of the eye would be affected by the drug," Srivastava said.

The discovery is published in the October issue of Investigative Ophthalmology and Visual Science. (ANI)