posted August 10, 2000 07:55 PM            

More Light Shed on Cataract Formation,
Including Glaucoma Drug Link

by Jim Dryden
Contact:
Washington University
School of Medicine
in St. Louis
Jim Dryden
314-286-0110

Cataracts are a common cause of vision loss in older adults. About half of Americans ages 65 to 74 develop cataracts, and 70 percent of those over 75 have them. They result partly from exposure to the ultraviolet B (UVB) rays in sunshine. Now, researchers at Washington University School of Medicine in St. Louis have identified a potentially key link between cataracts and light exposure. They also suspect that a new glaucoma drug may have the unintended effect of promoting cataracts.

The researchers report that fatty acids called prostaglandins are involved both in the creation and progression of cataracts, and that they have prevented cataracts by inhibiting prostaglandin synthesis.
Unfortunately, they also have found that one of the prostaglandins that resembles a new glaucoma drug, may promote cataract formation. The drug, called latanoprost, can lower pressure in the eye and delay damage from glaucoma, but the researchers worry that it might have the unintended side effect of creating cataracts or increasing their severity.

A cataract is a clouding of the lens of the eye that obstructs the passage of light. Although cataract patients can be treated surgically, the researchers say a better understanding of how cataracts form might lead to methods that prevent the development of cataracts.
Reporting in the July 1996 issue of the journal of Investigative Ophthalmology and Visual Science, a research team led by Usha P. Andley, Ph.D., assistant professor of ophthalmology and visual sciences and of biochemistry and molecular biophysics, confirms that exposure of rabbit eyes to UVB led to cataract formation. But the team also showed that, even in the presence of large doses of UVB, inhibiting prostaglandin synthesis prevented the cataracts. Andley is a Research to Prevent Blindness Robert E. McCormick Scholar.

"We had known for many years that UVB rays are involved, but we did not know how they change the chemical makeup of the lens," Andley explains. "We have shown in this study that prostaglandin synthesis increases in response to UVB radiation. We also showed that, when we inhibit prostaglandin synthesis, we prevent cataracts."
Andley's team is the first to show that inhibition of prostaglandin synthesis in the eye can prevent or lessen the severity of cataracts.

"We used nonsteroidal anti-inflammatory drugs," says co-investigator Bernard Becker, M.D., professor emeritus of ophthalmology and visual sciences. "Drugs such as aspirin and ibuprofen work in part because they inhibit prostaglandin synthesis. In this study in rabbits, we used a nonsteroidal drug called indomethacin. Sure enough, it inhibited the synthesis of prostaglandins and prevented cataracts in eyes exposed to UVB."
The researchers identified two particular prostaglandins activated by UVB radiation. The concentration of the first, called PGE2, increased 100-fold following UVB exposure. A second, called PGF2a, was present at 30 times its former concentration after the eye was exposed to UVB.

"Initially we thought that PGE2 was our main problem because it was present in such large amounts," Andley recalls. "So to test that idea, we exposed eyes to high concentrations of PGE2, concentrations similar to the level that would be created by UVB exposure, but when we added the PGE2, we did not create cataracts."
In fact, they learned that PGE2 had a protective effect. When the researchers treated eyes with PGE2 and exposed them to UVB no cataract formed. Andley suspects PGE2 may be synthesized in large amounts to protect the lens from UVB exposure. PGF2a, however, increases the severity of cataracts.

"In this model it was clear that PGF2a was the real culprit," Becker explains. "When the eyes, exposed to UVB were treated with the prostaglandins, PGE2 prevented the development of cataracts, and PGF2a failed to do so."

Culprit Ingredient in Glaucoma Drug
Andley says there is much to learn about prostaglandin synthesis and cataract formation but that it is apparent that prostaglandins, especially PGF2a, are important in cataracts. That discovery is a cause for concern among some ophthalmologists because a derivative of PGF2a is the principal ingredient in a new glaucoma drug.

Most patients with glaucoma have increased pressure in the eye. The standard treatment is to use medications to lower pressure. One such drug, latanoprost, now includes a derivative of PGF2a. It is very good at lowering intraocular pressure, but Becker, a pioneer in the treatment of glaucoma, worries that it may solve one problem while creating another.
"Our concern -- though we were using a rabbit model and much higher concentrations of PGF2a -- is that the long-term use of PGF2a derivatives in patients with glaucoma might aggravate cataract development," he says.

Becker admits that most glaucoma patients are elderly and that many might develop cataracts anyway. But he says clinicians should be aware of the potential complications before starting their patients on prostaglandin therapy for glaucoma.
As for the differences between human and rabbit eyes, Andley says that both PGE2 and PGF2a are found in human eyes. So she suspects that both are synthesized in human eyes in response to UVB exposure just as they are in the rabbit model.

"We suspect that if we could block PGF2a production, we could perhaps prevent cataracts," Andley says. She also stresses that researchers need to learn more about the steps between prostaglandin synthesis and cataract formation before testing such a strategy in humans.
"Cataracts form over a long period of time," she says. "Our experiments used high doses of UVB and high doses of prostaglandins. We need to make sure that long-term, low-dose exposure causes similar reactions before we can even think about studies in humans."

I don't know if using PGF2a will affect us or not. Sounds like it happens anyway... but who knows.. maybe this will increase our chances of our eyes going out.
Oh well.. by then, I won't wanna see my body anyway!!!

posted August 10, 2000 07:59 PM            

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"The race is long... and in the end, it's only with yourself."

"The greatest risk is not taking one."

posted August 10, 2000 10:40 PM            

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It's All Good Bro's!!!

Ranger

posted August 11, 2000 03:30 AM         

Thanks guys. good info

Dutch

posted August 11, 2000 04:51 PM            

Don't worry Swol, it took me 2-3 weeks before I needed the bathroom. I think it will come. Give it some time.

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Jeff

Don't look back, life is too short