Recent experiments in rats have elucidated the mechanism of action underlying uveitis, one of the world's leading causes of blindness in humans, and have identified a new avenue for its treatment. Uveitis, inflammation of the tissue layer below the outer surface of the eye (uvea), which includes the iris, can be caused by autoimmune disease, infection or toxin exposure. It is the primary cause of severe visual impairment in humans, accounting for 5–15% of cases of total blindness in the US and a higher proportion of those cases in developing countries.

Current treatment for uveitis is immune suppression via steroids or other drugs, which can have unwanted side effects and should not be used long-term. This is a particular concern for uveitis associated with autoimmune disorders, because these cases require long-term treatment.

Kota V. Ramana and colleagues at the University of Texas Medical Branch (Galveston) searched for non-steroidal means of reducing the inflammation in uveitis. They worked with a rat model of uveitis called endotoxin-induced uveitis (EIU), which is thought to represent certain types of human uveitis. EIU is induced in rats by subcutaneous injection of lipopolysaccharide. Ramana and his group targeted the inflammation signaling pathway and found that inhibition of aldose reductase (AR), an enzyme involved in producing inflammatory signaling molecules, suppressed ocular inflammation in EIU rats (Invest. Ophthalmol. Vis. Sci., 48, 4634–4642; 2007). Leukocyte infiltration, protein leakage into the aqueous humor and expression of several markers of inflammation in eye tissues were all reduced in EIU rats treated with an AR inhibitor compared with EIU rats not given the inhibitor.

These results suggest that inhibition of AR might hold promise for reducing ocular inflammation in human disorders such as uveitis. This potential represents a new treatment approach, and Ramana and his colleagues hope their research will progress to clinical trials.

They used an AR inhibitor called zopolrestat, which is currently undergoing phase 3 clinical trials as a treatment for diabetic complications and has shown no major side effects so far. Other AR inhibitors would probably have similar effects on ocular inflammation. If clinical trials for uveitis do take place and have positive results, Ramana's group intends to develop an eye-drop formulation of zopolrestat to deliver the treatment directly to the tissues of the eye.