Tuesday, September 30, 2014

Resveratrol and the Eye

Within the last decade, the discovery of red wine as a proponent for increased cardiovascular health has been prominent in science-related media . The compound in question is called “Resveratrol,” and its ability to lead the consumer to a longer, healthier life has been controversial due to lack of reproducible results of Dr. David Sinclair, molecular biologist at Harvard Medical School and founder of Sirtis (SIRT research).

Upon clarification by more recent research, Resveratrol is thought to boost activity of the enzyme SIRT1, in conjunction with a bulky hydrophobic amino acid residue, to de-acetylate proteins involved in aging and metabolism. Resveratrol acts on a wide variety of proteins, and the full extents of its effects are still to be determined.

More recently, researchers have been exploring the use of resveratrol in other areas of health, namely in the reduction of ocular hypertension (OHTN). Systemic, topical, periocular, or intravitreal use of steroids (as therapy for ailments of the eye) can lead to onset of OHTN, which can then lead to glaucoma. Current therapies are not effective in reducing intra-occular pressure (IOP) and often cause negative effects systemically and locally, so there has been a push to develop better treatment options for patients suffering from OHTN. A recent study has successfully used resveratrol to reduce IOP in rats.

The experiment was two-part: IOP reduction by resveratrol in normotensive rats, and IOP reduction by resveratrol in steroid-induced OHTN rats. Both the normotensive and OHTN groups tested a vehicle (control) solution in one eye. A vehicle solution contains everything that the drug solution contains, except the drug; in this case, the vehicle contained 3% polyvinylpyrrole (PVP), which was used to dissolve the resveratrol in the drug solution. The drug solution contained trans-resveratrol, which is the more biologically active conformation of the compound (as compared to cis-resveratrol).


The study showed that application of trans-resveratrol was effective in reducing IOP in both the normotensive and steroid-induced OHTN rats. In both sets of rats, 0.2% trans-resveratrol achieved peak IOP reduction: 15.1% reduction in the normotensive rats and 25.5% reduction in the OHTN rats. This study lends possibility to new treatments for OHTN, but also to untapped uses of resveratrol in the eye. I will actually be exploring one of these uses in an Opthalmology lab at the Anschutz Medical Campus—I’ll be testing the effect of resveratrol on dry eye in a murine model.

2 comments:

  1. I like your topic choice, Tamara! I briefly mentioned resveratrol in my blog post as well, discussing it's anti-angiogenic properties, or it's inhibition of abnormal vessel formation. Do you (or does anyone) believe that resveratrol's anti-angiogenic properties could play a role in the reduction of intra-occular pressure? Or is there another mechanism at work? (Sorry, I could not access the link to the study, maybe it discusses this...) After a bit of research, I see that glaucoma and IOP are caused by overproduction/inadequate flow of the aqueous humor in the eye, thereby causing OHTN--I wonder if the vessels of the eye are connected to this in any way and if resveratrol helps to control this...

    (http://www.merckmanuals.com/home/eye_disorders/glaucoma/glaucoma.html?qt=glaucoma&alt=sh)

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  2. What I always wonder with studies such as the one that you're doing is: Does this actually work? Can we compare what happens on a mouse model (externally) to what happens on a mouse model had it been given it through dietary supplementation? Which of these modes more accurately mirrors what happens in the human body?

    Here's a real question for you: Do you think that people that are genetically predisposed to OHTN could counteract their genetics by drinking red wine? How effective is resveratrol, do I need to drink a glass of red wine a day or four glasses to start my fight against OHTN and glaucoma? Why is it only found in red wine? Does this mean that grapes that produce red wine are better for eye health than grapes that produce white wine (not including of course the fermentation process of wine).

    Lot's of questions, but it's an interesting conversation and it's interesting that the research for red wine was at first, non-duplicatable (yes, I decided to make my own word similar to that of the history of the word muggle).

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