Antioxidant supplementation may lower risk of Oxidative stress induced glaucoma: Study

Treatment for glaucoma most commonly involves therapy to reduce intraocular pressure (IOP). However, disease progression persists in some patients even after IOP is successfully reduced.

Oxidative stress has three key effects in glaucoma. First, it raises IOP by altering the trabecular meshwork and impairing aqueous humor outflow. Second, it disrupts autoregulation of blood flow to the optic nerve by altering the vessels that feed it. Finally, patients with a low antioxidant level in the eye are also susceptible to systemic oxidative stress, which can induce RGC death.

Himori et al carried a study giving a daily dietary antioxidant supplement over 8 weeks to patients with glaucoma. The supplement was developed and first reported by Maekawa et al, who identified the components of the supplement through screening and reported that three food-derived compounds, hesperidin, Tamarindus indica, and crocetin, had a protective effect in a primary culture of retinal cells under oxidative stress.

This study had a prospective, single arm design. Thirty Japanese glaucoma patients were recruited and given 4 tablets with ample water twice a day for 8 weeks. The treatment was stopped, and the subjects were followed for an additional 8 weeks. Authors measured biological antioxidant potential (BAP) with a free radical analyzer. Study also measured urinary 8-hydroxy-2ʹ-deoxyguanosine (8-OHdG; a marker of oxidative DNA damage). Clinical laboratory data were measured in venous blood samples. Clinical parameters were also recorded.

The 8-OHdG level was not reduced. Authors also divided the patients into groups with high or low oxidative stress.

In patients with relatively high oxidative stress, the 8-OHdG level was significantly reduced at weeks 4, 8, 12, and 16 (P < 0.001, P < 0.01, P < 0.01, P < 0.01), and BAP was significantly elevated at weeks 8 and 12 (P = 0.03, P = 0.04).

In patients with relatively low oxidative stress, the 8-OHdG level was not significantly reduced during supplement intake but was significantly elevated at weeks 12 and 16 (P =0.03, P = 0.04), while BAP was not significantly elevated.

The results of this study are of particular interest for the treatment of patients with a low antioxidant level; authors found that antioxidant supplementation may be an effective option for such patients. This is especially promising for the treatment of glaucoma, an age-related chronic neurodegenerative disease in which oxidative stress has been shown to play an important role.

The glaucoma patients in this study who had a relatively higher level of oxidative stress and took a daily antioxidant supplement showed an increase in BAP and a decrease in 8-OHdG, while the glaucoma patients with a relatively lower level of oxidative stress who took the supplement did not show an increase in BAP and showed a decrease in 8-OHdG. This suggests that this supplement was only effective in patients with a high oxidative stress level.

Hesperidin had these effects in vivo in mice, reducing oxidative stress and preventing RGC death caused by N-methyl D-aspartate (NMDA)-induced excitotoxicity. Tamarindus indica is indigenous to tropical Africa. It is high in tartaric acid, B vitamins, and minerals. It has antioxidant, anti-inflammatory, anti-diabetic and anti-atherosclerotic effects. Crocetin is a natural apocarotenoid dicarboxylic acid that is found in the crocus flower and in Gardenia jasminoides. Crocetin has various effects, acting as an antioxidant and anti-inflammatory and can inhibit the caspase pathway, preventing retinal damage induced by NMDA. These results suggest that these three food-derived compounds, used as a dietary supplement, might help reduce RGC degeneration in retinal disease.

This study indicates that patients with a low systemic antioxidant level may have increased susceptibility to oxidative stress, which might accelerate the progression of glaucoma. Oxidative stress may be a key non-IOP risk factor for age related cataracts and glaucoma.

"Our study revealed that antioxidant supplementation was effective in patients with high oxidative stress level, suggesting that such supplementation may be a novel way of combating diseases induced by systemic oxidative stress, and could contribute to individualized treatment for these diseases."

Source: Himori et al; Clinical Ophthalmology 2021:15 2293–2300