University of Texas Medical Branch at
Galveston researchers have discovered that a drug already prescribed to
millions of people with diabetes could also have another important use:
treating one of the world's leading causes of blindness.
In
laboratory rat and cell-culture experiments, the scientists found that metformin, which is
commonly used to control blood sugar levels in type 2 diabetes, also
substantially reduced the effects of uveitis, an inflammation of the
tissues just below the outer surface of the eyeball.
Uveitis
causes 10 to 15 percent of all cases of blindness in the United States, and is
responsible for an even higher proportion of blindness globally. The only
treatment now available for the disorder is steroid therapy, which has serious
side effects and cannot be used long-term.
"Uveitis
has various causes — the most common are infectious diseases and autoimmune
disorders— but they all produce inflammation within the eye," said UTMB
professor Kota V. Ramana, senior author of a paper on the study now online in
the journal Investigative Ophthalmology & Visual Science.
"Metformin inhibits the process that causes that inflammation."
The
scientists discovered metformin's efficacy when they tested it in rats given an
endotoxin that mimicked the inflammatory effects of bacterial infection. The
results showed clearly that metformin was a very effective anti-uveitis agent.
"We
found that the drug is therapeutic as well as preventive — if we gave our rats
the drug beforehand, they didn't develop uveitis, and if we gave it after
uveitis had developed, it was therapeutic," said UTMB professor Satish
Srivastava, also an author of the IOVS paper. "Metformin's strong
anti-inflammatory properties make this possible."
According
to the researchers, metformin works by activating an enzyme called AMPK, which
in turn damps down the activity of the protein NF-kappa B. The inhibition of
NF-kappa B suppresses the production of inflammatory signaling molecules —
cytokines and chemokines — needed to initiate and sustain uveitis.
Because
metformin is already used so widely as a therapy for diabetes, the UTMB
scientists believe that it has a good chance of being rapidly adopted as an
anti-uveitis drug.
"I
think after a few more pre-clinical studies are done, we can get this drug to
patients in a shorter time than usual," Ramana said. "Its safety is
already known, so all that we need to see is its efficacy in humans."
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