Anthocyanins May Benefit Open Angle Glaucoma by Normalizing ET-1

Anthocyanins Improve Ocular Blood Flow, Slow Visual Field Decline in Glaucoma

Anthocyanins are a type of dietary flavonoid found in bilberries, black currants, and other red and purple berries and grapes. These flavonoids possess direct antioxidant activity, decrease inflammation, effect cell-signaling pathways, and promote vasodilation. Orally administered anthocyanins have been shown to accumulate in ocular tissues, including the retina, choroid and ciliary body.

Previously, researchers at Sapporo Medical University in Japan evaluated the effects of anthocyanins on disease progression of open angle glaucoma (OAG) in a randomized, placebo-controlled, 2-year trial.

The study subjects had been treated for more than 2 years by anti-glaucoma drops, had IOP measured every 1-2 months, and had undergone visual field testing (Humphrey visual field 30-2 test) every 3-6 months prior to entering the study.

The results, published in 2012 (1), showed that anthocyanins slow down visual field deterioration and improve ocular blood flow.

The deterioration of the Humphrey visual field mean deviation at 24 months was significantly less in patients receiving anthocyanins (50 mg daily from black currant extract) compared to placebo-treated patients. Additionally, ocular blood flow (at the optic nerve head, its rims and surrounding retina) significantly increased relative to the placebo group.

Based on these findings, the same research team initiated the present study to clarify the mechanisms by which anthocyanins induced these effects (2).

Study Design

During the original 2-year trial, serum samples were obtained from participants every 6 months. These samples were separated into those from the anthocyanin and placebo groups. Serum samples were also acquired from age and gender matched healthy volunteers, who served as a control.

Concentration of serum endothelin-1 (ET-1), nitrite (NO2-) and NO2- + nitrate (NO3-) levels, advanced protein oxidation products, and antioxidant activities were measured using commercially available kits.

Results

At baseline in the original trial, serum ET-1 concentrations were significantly lower in patients with OAG compared to healthy controls.

During the 24-month treatment period, ET-1 in the active group increased to levels seen in healthy volunteers. In contrast, ET-1 in the placebo group remained at levels lower than in controls over the study period.

All other serum measurements in OAG patients were comparable to those seen in controls, and no significant changes in these measures were seen over time in either the anthocyanin or placebo groups.

Comments

The authors conclude that one action of anthocyanins in this population of glaucoma patients is to normalize abnormal levels of ET-1.

ET-1 is a potent vasoconstrictor believed to play a role in local auto-regulation of blood flow. One receptor for ET-1, ETA, is mainly present on vascular smooth cells and is responsible for the vaso-constriction caused by ET-1. Another receptor, ETB, is found primarily on the vascular endothelium and is believed to produce transient vasodilatation through release of nitric oxide.

The authors believe that anthocyanins normalize serum ET-1 levels by stimulating the ETB receptors. In turn, this may cause an increase in ocular blood flow and slow down glaucoma progression.

References

1. Ohguro H, et al. Two-year randomized, placebo-controlled study of black currant anthocyanins on visual field in glaucoma. Ophthalmologica 228:26–35, 2012.
2. Yoshida K, et al. Black currant anthocyanins normalized abnormal levels of serum concentrations of endothelin-1 in patients with glaucoma. J Ocul Pharmacol Ther 29:480-87, 2013.