Suppression of Oxidative Stress as Potential Therapeutic Approach for Normal Tension Glaucoma

Harada, Chikako; Noro, Takahiko; Kimura, Atsuko; Guo, Xiaoli; Namekata, Kazuhiko; Nakano, Tadashi; Harada, Takayuki

doi:10.3390/antiox9090874

Cited by 25 publications

(39 citation statements)

References 81 publications

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“…Indeed, although IOP elevation is known as one of the most recurrent risk factors for glaucoma ( Nickells et al, 2012 ) and is the main target of pharmaceutical treatments ( Stein et al, 2021 ), often it could manifest only at late stages of the disease or may not occur, as in the case of normotensive glaucoma ( Weinreb et al, 2014 ). Similar to diabetic retinopathy, oxidative stress is likely to represent a major trigger also for glaucoma ( Domènech and Marfany, 2020 ; Garcia-Medina et al, 2020 ; Harada et al, 2020 ; Wang et al, 2020 ), and LG, which does not have any effect on the rise of IOP characteristic of D2 mice, is likely to exert its protective effect thanks to its powerful antioxidant properties.…”

Section: Discussionmentioning

confidence: 99%

The Potential of Lisosan G as a Possible Treatment for Glaucoma

et al. 2021

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Lisosan G (LG), a fermented powder obtained from whole grains, is a nutritional supplement containing a variety of metabolites with documented antioxidant properties. We have recently demonstrated that orally administered LG protects diabetic rodent retinas from oxidative stress, inflammation, apoptosis, blood-retinal barrier disruption, and functional damage. Here, we investigated whether LG may exert protective effects in a model of glaucoma and measured the amounts of selected LG components that reach the retina after oral LG administration. Six-month-old DBA/2J mice were given an aqueous LG solution in place of drinking water for 2 mo. During the 2 mo of treatment with LG, the intraocular pressure (IOP) was monitored and the retinal ganglion cell (RGC) functional activity was recorded with pattern-electroretinography (PERG). At the end of the 2-mo period, the expression of oxidative stress and inflammatory markers was measured with qPCR, and RGC survival or macroglial activation were assessed with immunofluorescence. Alternatively, LG was administered by gavage and the concentrations of four of the main LG components (nicotinamide, gallic acid, 4-hydroxybenzoic acid, and quercetin) were measured in the retinas in the following 24 h using mass spectrometry. LG treatment in DBA/2J mice did not influence IOP, but it affected RGC function since PERG amplitude was increased and PERG latency was decreased with respect to untreated DBA/2J mice. This improvement of RGC function was concomitant with a significant decrease of both oxidative stress and inflammation marker expression, of RGC loss, and of macroglial activation. All four LG metabolites were found in the retina, although with different proportions with respect to the amount in the dose of administered LG, and with different temporal profiles in the 24 h following administration. These findings are consistent with neuroenhancing and neuroprotective effects of LG in glaucoma that are likely to derive from its powerful antioxidant properties. The co-occurrence of different metabolites in LG may provide an added value to their beneficial effects and indicate LG as a basis for the potential treatment of a variety of retinal pathologies.

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Section: Discussionmentioning

confidence: 99%

The Potential of Lisosan G as a Possible Treatment for Glaucoma

et al. 2021

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“…This model shows glaucomatous phenotypes such as RGC loss, optic nerve atrophy, and visual impairment while maintaining normal IOP [ 3 , 4 ]. Although the early onset of RGC degeneration in GLAST +/- mice is atypical compared with human glaucoma, it may be an advantage to carry out basic experiments in a short span of time [ [3] , [4] , [5] , [6] , [7] , [8] ]. We first examined the effects of lighting environment in GLAST +/- mice and found that RGC degeneration started before 3 weeks old in the Dark/Dark condition.…”

Section: Discussionmentioning

confidence: 99%

“…Since glutathione has a strong anti-oxidative effect, both glutamate neurotoxicity and oxidative stress may be involved in RGC degeneration in GLAST-deficient mice. On the other hand, intraocular pressure (IOP) in GLAST-deficient mice was not increased compared with wild-type mice, thus these mice may be utilized as a model of normal tension glaucoma [ [5] , [6] , [7] , [8] ].…”

Section: Introductionmentioning

confidence: 99%

Effects of lighting environment on the degeneration of retinal ganglion cells in glutamate/aspartate transporter deficient mice, a mouse model of normal tension glaucoma

Ōhashi

Namekata

Guo

et al. 2022

Biochemistry and Biophysics Reports

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Lighting conditions may affect the development of retinal degenerative diseases such as macular degeneration. In this study, to determine whether the lighting environment affects the progression of degeneration of retinal ganglion cells (RGCs), we examined glutamate/aspartate transporter (GLAST) heterozygous (GLAST +/- ) mice, a mouse model of normal tension glaucoma. GLAST +/- mice were reared under a 12-h light-dark cycle (Light/Dark) or complete darkness (Dark/Dark) condition after birth. The total RGC number in the Dark/Dark group was significantly decreased compared with the Light/Dark group at 3 weeks old, while the number of osteopontin-positive αRGCs were similar in both groups. At 6 and 12 weeks old, the total RGC number were not significantly different in both conditions. In addition, the retinal function examined by multifocal electroretinogram were similar at 12 weeks old. These results suggest that lighting conditions may regulate the progression of RGC degeneration in some types of glaucoma.

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“…17 In vivo experiments using animal models of glaucoma (based on apoptosis signal regulating kinase 1, valproic acid, N-acetylcysteine, spermidine, and coenzyme Q10) have showed that administering antioxidants had a neuroprotective effect. 18 These research suggest that antioxidants are a potential candidate for glaucoma therapy.…”

Section: Introductionmentioning

confidence: 98%

The Effect of Dietary Antioxidant Supplementation in Patients with Glaucoma

Himori

Yanagimachi

Omodaka

et al. 2021

OPTH

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Purpose Oxidative stress may be a risk factor for glaucoma, and many previous reports have suggested that antioxidants could be a promising treatment. Here, we investigated the effects of a novel supplement containing three food-derived antioxidants (hesperidin, crocetin, and Tamarindus indica ) on markers of oxidative stress in patients with glaucoma. Patients and Methods 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. We measured biological antioxidant potential (BAP) with a free radical analyzer. We 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. Comparisons used a one-way analysis of variance (ANOVA) followed by Dunnett’s test. Results The 8-OHdG level was not reduced. We 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. Conclusion An 8-week oral course of antioxidant supplementation was effective in patients with a high oxidative stress level. Dietary supplementation could hold promise in the treatment of systemic oxidative stress-related diseases.

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Suppression of Oxidative Stress as Potential Therapeutic Approach for Normal Tension Glaucoma

Cited by 25 publications

References 81 publications

The Potential of Lisosan G as a Possible Treatment for Glaucoma

The Potential of Lisosan G as a Possible Treatment for Glaucoma

Effects of lighting environment on the degeneration of retinal ganglion cells in glutamate/aspartate transporter deficient mice, a mouse model of normal tension glaucoma

The Effect of Dietary Antioxidant Supplementation in Patients with Glaucoma

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