Large molecule metabolites of Resveratrol found to pass blood-ocular barrier

Inability to obtain biopsy specimens from tissues in the brain and eyes of humans had previously thwarted confirmation of resveratrol or its metabolites in nervous tissues.

Researchers at Tongji Medical College at the Huazhong University of Science & Technology in Wuhan/Hubei Province in China confirm that metabolites of resveratrol (Longevinex®) are found in ocular tissues from the outer (conjunctiva) and inner (aqueous fluid, vitreous gel) of the human eye following oral consumption. Resveratrol itself could only be detected in the conjunctiva, a clear tissue that lines the inside of the eyelids and the sclera (white of the eyes).

Tissue samples from the front and back of the inner eye were obtained directly from patients undergoing eye surgery after retinal detachment. Tissue samples were obtained from the outer eye (conjunctiva), aqueous fluid in the front of the inner eye and from the vitreous gel that fills the back of the eyes.

Blood-brain/blood-ocular barriers

While the red wine molecule resveratrol continues to astound biologists, exerting profound beneficial health effects in tissues throughout the human body, the question as to whether resveratrol or its metabolites pass through semipermeable blood/brain and blood/ocular barriers to exert biological activity had thrown a scientific cloud over application of resveratrol in humans, until now.

Researchers have demanded more evidence of the biological mechanisms of resveratrol before recommendation as a dietary supplement.

Nervous tissues in the eyes and brain are specially protected from foreign substances (germs, inflammatory agents, toxins) by tightly packed cells in the smallest blood vessels (capillaries) that block entry of large molecules. In this manner large molecules are blocked from entering nervous system.

Over 100 years ago it was discovered if that if blue dye is injected into the bloodstream, tissues throughout the human body turn blue, except the brain, spinal cord and the eyes. [Washington University] These are called the protective blood-brain and blood-ocular barriers.

The human eye has two barriers, the blood-aqueous barrier in the front of the inner eye and the blood-retinal barrier at the back of the eyes. [Survey of Ophthalmology 1979]

In prior laboratory studies resveratrol was shown to not only penetrate the blood-brain barrier but actually help maintain the integrity of this barrier. [Journal Neurophysiology Nov 2016]

Tissue delivery

In prior studies the presence of resveratrol has been shown in various major organs (liver, kidneys, lungs and heart). While resveratrol is a small molecule (molecular weight 228 Daltons), it is conjugated (attached) to larger detoxification molecules (sulfate, glucuronate) in the gut and liver. Therefore, its direct passage as a free unbound small molecule into nervous tissues has been called into question.

Resveratrol is rapidly metabolized directly in the gut (intestines) and after oral absorption in the liver.

Human Applications

An earlier study by the same researchers showed resveratrol (Longevinex®) works beneficially by its ability to expand (dilate) blood vessels at the back of the eyes thus improving circulation. [Current Eye Research Oct 2016]

In preliminary case reports, resveratrol (Longevinex®) has been shown to rescue helpless patients with advanced retinal problems and restore vision. [Nutrients Oct 2014]

Resveratrol and its metabolites have also recently been shown to protect the retina of the eyes from toxic blue light. [Archives Pharm Research Dec 2016]

A topically applied resveratrol eye drop may be closer to entering human trials after it was shown to sustain a reduction in intraocular fluid pressure that can damage the optic nerve at the back of the eyes. [Experimental Eye Research Dec 2016] Oral consumption of resveratrol has also been shown to exert similar protective properties for the optic nerve. [Neurobiology Aging May 2016]

Resveratrol has also been shown to inhibit the formation of abnormal blood vessels at the back of the eyes. [Investigative Ophthalmology April 2011]

Immediate bioavailability

While this most recent study showed only resveratrol metabolites (sulfate, glucuronate) are detected in the inner eye, the inclusion of resveratrol with quercetin is said to permit more free unbound resveratrol to initially pass through the liver before it is metabolized. [Xenobiotica 2000]

In another astonishing animal study resveratrol was metabolized in the gut (intestines) to favorably influence the balance of gut bacteria and indirectly inhibit the accumulation of atherosclerotic arterial plaque. [MBio April 2016] So at least for some tissues in the body, questions over resveratrol's absorption and bioavailability may be a moot point.

Not all eyes exhibited resveratrol or its metabolites after oral consumption, which is an obvious area for further investigation