Glaucoma and Antioxidants: Review and Update
Abstract
:1. Introduction
2. Antioxidant Supplementation in Animal Models of Glaucoma
3. Antioxidant Supplementation in Clinical Trials in Glaucoma
4. Discussion and Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Year of Publication | Authors [Reference] | Investigated Animals | Used Antioxidant | Results |
---|---|---|---|---|
1989 | Das et al. [12] | Wistar rat. | Vitamin A (retinol) | Inhibition of lipid peroxidation in rat brain homogenates. |
2002 | Chidlow et al. [13] | Wistar rat. | α-lipoic acid | Reduction of ganglion cell death after ischemia. |
2004 | Hirokaa et al. [14] | Sprague-Dawley rat. | Ginkgo biloba | Reduction in retinal ganglion cell loss in eyes with chronic, moderately elevated IOP. |
2005 | Eckert [15] | Review: a variety of cell cultures from different sources. | Ginkgo biloba | Stabilisation and protection of mitochondrial function of TC12 cells in culture. |
2006 | Nguyen et al. [16] | Sprague-Dawley rat. | Omega 3 | Decrease in IOP associated with a significant increase in outflow facility and a decrease in ocular rigidity. |
2007 | Nucci et al. [17] | Wistar rat. | Coenzyme Q10 | Reduction of glutamate and of retinal ganglion cell apoptosis after ischemia-reperfusion. |
2008 | Nakajima et al. [18] | RGC-5, (a rat ganglion cell-line transformed using E1A virus) rat. | Coenzyme Q10 Troxol (soluble vitamin E derivative) | Reduction of retinal ganglion cell (in culture) damage and apoptosis induced by hydrogen peroxide and NMDA. |
2008 | Russo et al. [19] | Rat (unspecified strain). | Coenzyme Q10 NMDA receptor antagonists Nitric oxide synthesis inhibitors | Review: Coenzyme Q10, NMDA receptor antagonists and nitric oxide synthesis inhibitors afford retinal protection supporting an important role for excitotoxicity in the mechanisms underlying retinal ganglion cell death. |
2009 | Gionfriddo et al. [20] | DBA/2J mice. | Alfa-luminol | Prevention of decrease in glutamate, glutathione and glutamine synthetase. |
2009 | Schnebelen et al. [21] | Sprage-Dawley rat | Omega-3 Omega-6 | A supplementation of combined fatty acids is more effective than individual supplementation in preventing retinal damage due to increased intraocular pressure. |
2010 | Ko et al. [22] | Wistar rat. | Vitamin E | Increase in lipid peroxidation and elevated concentration of glutathione in vitamin E deficient rats compared to controls. |
2012 | Cybulska-Heinrich et al. [23] | Rat (unspecified strain) and human. | Ginkho Biloba | Review about the mechanisms mediating the beneficial effects on animal models of glaucoma and also in human patients. |
2013 | Inman et al. [24] | DBA/2J mice. | α-lipoic acid (ALA) | Increase antioxidant gene and protein expression, increase protection of RGCs and improved retrograde transport in treated subjects compared to control. |
2014 | Lee et al. [25] | DBA/2J mice. | Coenzyme Q10 | Promotion of retinal ganglion cell survival and preservation of axons in the optic nerve head in glaucomatous DBA/2J mice. |
2014 | Xu et al. [26] | Porcine TM cells in culture. | Vitamin C (Ascorbic Acid) | Antioxidant properties with lower ferritin and basal iROS (intracellular reactive oxygen species) content, induction of autophagy, as well as increased lysosomal proteolysis in trabecular meshwork cells. |
2015 | Can et al. [27] | Sprague-Dawley rat. | Ghrelin | Decrease in apoptosis and related proteins: expression of GFAP (glial fibrillary acidic protein), S-100, and vimentin compared to control group. Reduction of oxidative and nitrosative stress. |
2015 | Iomdina et al. [28] | Male pigmented rabbit. | 10-(6′-plastoquinonyl) decyltriphenylphosphonium (SkQ1) | Reduction of IOP and preservation of optical nerve axons. |
2015 | Hsu et al. [29] | Beagle dog. | Vitamin E | Greater and longer lasting decrease of IOP using contact lenses coloaded with timolol, dorzolamide and vitamin E compared with timolol and dorzolamide-loaded lenses or eye drops. |
2016 | Pirhan et al. [30] | Wistar rat. | Riluzol and Resveratrol | Preservation of retinal ganglion cells in all treated groups of rats with chronic elevation of IOP induced by intracameral injection of hyaluronic acid. |
2017 | Williams et al. [31] | DBA/2J mice. | Vitamin B3 | Protection prophylactically and as an intervention against mitochondrial vulnerability and optic nerve degeneration. |
2017 | Davis et al. [32] | Primary murine (C57BL/6) retinal mixed cultures (pMC) and an immortalised retinal neuronal (RN) cell line (RGC5). Adult male Dark Agouti (DA) rats. | Coenzyme Q10 | Reduced detection of apoptotic retinal cells in both in vitro and in vivo-treated groups when compared to control. |
2018 | Luo et al. [33] | Sprague-Dawley rat. | Resveratrol | Reduced retinal damage and retinal ganglion cell loss after retinal ischemia-reperfusion. |
2018 | Zhang et al. [34] | Sprague-Dawley rat. | Resveratrol | Decrease the cell apoptosis, mitochondrial dysfunction and radical oxygen species generation both in vitro and in vivo experiments, and normalised retinal morphology in vivo. |
2019 | Yang et al. [35] | Adult Fischer F344 rat. | Green tea extract | Higher number of surviving retinal ganglion cells, less apoptotic RGCs, smaller constricted pupil area and reduction of inflammation and apoptosis-related protein expressions. |
2019 | Wu et al. [36] | Spray-Dawley rat. | Szeto-Schiller peptide 31 (SS-31) | Neuroprotective effects by reducing oxidative stress and inhibiting mitochondrial-mediated apoptosis. |
2019 | Angel Aillegas et al. [37] | New Zealand rabbit. | Ascorbyl Laurate (ASC12) | Increment in kinetic antioxidant capacity in the aqueous humour of normotensive and hypertensive rabbits. |
2020 | Cao et al. [38] | C57BL/6JJcl mice. | Resveratrol (RSV) | Strong cytoprotective action against cell death through multiple pathways under high IOP. |
2020 | Chou et al. [39] | DBA/2J mice. | Vitamin B | Preservation of retinal ganglion cell function, density and mitochondria. |
2020 | Tanaka-Gonome et al. [40] | GLAST-/-and C57BL/6J mice. | Astaxanthin (AST) | Attenuation of the thinning of ganglion cell complex in a model of normal tension glaucoma. |
Year of Publication | Author | No. of Participants/Treatment | Antioxidant Substance | Results |
---|---|---|---|---|
1999 | Cellini et al. [41] | 40 ocular hypertensive patients (2 groups: treated versus placebo) | Omega-3 polyunsaturated fatty acids | Improvement mean defect (MD)with blue7yellow perimetry |
2003 | Quaranta et al. [42] | 27 patients received 40 mg of GBE, taken orally, three times a day for 4 weeks, followed by an 8-week washout period, then 4 weeks of placebo treatment. Other patients underwent the same regimen, but took the placebo first and the GBE in the end. | Ginkgo biloba (GBE) | After treatment with GBE, a significant improvement in the indices of the visual fields. There were not found changes significant in the intraocular pressure, the blood pressure or heart rate after the placebo treatment or GBE |
2009 | Falsini et al. [43] | 18 patients with hypertension and 18 patients with glaucoma (OAG) were assigned to take placebo or epigallocatechin gallate (EGCG). | Gallate of epigalocatequina (EGCG) | Improvement of pattern electroretinogram (PERG’) in patients with open angle glaucoma but not in ocular hypertension. However, the perimetry automated standard showed no significant changes after EGCG or placebo |
2011 | Park et al., 2011. [44] | 30 NTG patients (2 groups: treated versus placebo) | Ginkgo biloba extract | Increased flow retinal blood peripapillary |
2012 | Shim et al. [45] | 302 patients, were divided into 3 groups, group 1 treated with Antianciokines, group 2 with GBE and group 3 were not treated (control group). | Ginkgo biloba extract (GBE) Antianciokines | After treatment with anthocyanins, the Average BCVA for all eyes got better from 0.16 (±0.34) a 0.11 (±0.18) units logMAR. After treatment with GBE, the deviation half of HVF improved from −5.25 (±6.13) to −4.31 (±5.60) |
2012 | Ohguro et al. [46] | 39 patients were divided into two groups, group 1 treated with blackcurrant (BCA) and group 2 treated with placebo. | Grosellanegra (BCA) | After administration BCAC, the flow ocular blood during the period of observation of 24 months increased compared to patients treated with placebo. However, significant changes were not observed in the conditions systemic and ocular, including IOP during the 24 month period |
2012 | Vetrugno et al. [47] | 97 patients, 52 in the treatment group and 45 in the control group. Patients were treated with a dietary supplement consisting of forskolin and rutin in addition to their pharmacological treatment. | Forskolina Rutin | All patients in the treatment group showed a further decrease of 10% (P < 0.01) of PIO. On the contrary, IOP values in the control group were stable from the beginning to the end of the treatment period. |
2013 | Ohguro et al. [48] | 21 patients, 12 were treated with BCAC and 9 were treated with placebo | Grosella negra (BCAC) | There was a decrease statistically significant in IOP mean at 2 weeks and 4 weeks, test paired) from the start in healthy treated subjects with BCA. However, this was not observed in the group treated with placebo. Oral administration of BCAC can induce a decrease beneficial in IOP levels in healthy subjects as well as in patients with glaucoma |
2013 | Egorov et al. [49] | 94 patients were divided into 3 groups: 50 patients received combined therapy with mexidol 100 mg and picamilon 150 mg, 22 patients received combined therapy with exidol 300 mg and picamilon 150 mg, 22 patients received only picamilon 150 mg | Mexidol Picamilon | Improvement was recorded in visual acuity, indications perimeter, electrophysiology and increase in the speed of blood flow |
2013 | Galbis-Estrada et al. [50] | Essential polyunsaturated fatty acids and antioxidants (Brusysec®) | Reduction of oxidative stress biomarkers (vascular endothelial growth factor, tumour necrosis factor α,interleukin-4, interleukin-6) subjective improvement of dry eye symptoms | |
2014 | Bonyadi Jabbarpoor et al. [51] | 34 angle glaucoma patients, 17 to receive 30 mg/day of aqueous saffron extract by mouth and 17 others received placebo treatment as a supplement of timolol and dorzolamide | Saffron extract | After three weeks of treatment, IOP decreased significantly to 10.9 ± 3.3 mmHg in the group of saffron in comparison with 13.5 ± 2.3 mmHg in the group at the end of the washing period, the IOP was 12.9 ± 3.0 in the saffron group versus 14.2 ± 2.0 mmHg in the control group (p = 0.175) |
2014 | Guo et al. [52] | 35 NTG patients (2 groups: treated versus placebo) | Ginkgo biloba extract | No effect on automated perimetry or sensitivity to contrast |
2015 | García-Medina et al. [53] | 35 patients NTG Oral supplementation versus placebo) | Two antioxidant formulas based on AREDS (antioxidants + minerals) with/without FA-3 PUFA | There are no differences significant among global indices perimeter, the RNFL peripapillary or the GCC macular at the beginning and at the end of the follow-up |
2016 | Mutolo et al. [54] | Complex composed of homotaurine, Coleus forskohlii root extract, Lcarnosine, folic acid, vitamins B1, B2, B6 and magnesium | We observe in patients treated a decrease in significant additional of the IOP and an improvement from the PERG amplitude to 6, 9, and 12 months, and sensitivity foveola 12 months | |
2018 | Harris et al. [55] | 45 patients treated, a group with the antioxidant and the other with placebo | Ginkgo biloba extract | Improvement in blood flow, a less vascular resistance in retina |
2018 | Romeo Villadoniga et al. [56] | 47 patients (23 treated with DHA and 24 untreated | Docosahexaenoico acid (DHA) | In the DHA group, the PIO, the content of erythrocytes increased by the DHA group and TAC levels increased compared to the untreated group |
2019 | Ozates et al. [57] | 64 patients (divided in two groups one treated with coenzyme Q10 and vitamin E and the other no treaty | Coenzyme Q10 Vitamin E | Mood levels lower watery in the group that was treated, same as one more level low superoxide dismutase. There were not significant changes observed in the level of malondialdehyde |
2019 | Quaranta et al. [58] | They will select a total of 612 patients | Coenzyme Q10 and Vitamin E | Improvement the already existing visual field damage in these patients. They achieved an MD reduction of 11.40 + 3.27 decibels (dB) compared to the 8.78 + 2.56 dB reduction in patients treated with placebo (p = 0.0001) |
2020 | Sanz-González et al. [59] | 30 patients, which were divided in two groups, one group of patients with glaucoma and a group healthy patients | R-alpha lipoic acid, taurine, vitamins C and E, lutein, zeaxanthin, zinc, copper and acid docosahexaenoic | After 6 months of supplementation, there was a significant increase in the total antioxidant status in plasma along with a parallel decrease in the group POAG. Malondialdehyde also decreased. Schirmer test improved (20–30%) and the subjective signs/symptoms of dry eye decreased notably in the POAG group in front of control group |
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Garcia-Medina, J.J.; Rubio-Velazquez, E.; Lopez-Bernal, M.D.; Cobo-Martinez, A.; Zanon-Moreno, V.; Pinazo-Duran, M.D.; del-Rio-Vellosillo, M. Glaucoma and Antioxidants: Review and Update. Antioxidants 2020, 9, 1031. https://doi.org/10.3390/antiox9111031
Garcia-Medina JJ, Rubio-Velazquez E, Lopez-Bernal MD, Cobo-Martinez A, Zanon-Moreno V, Pinazo-Duran MD, del-Rio-Vellosillo M. Glaucoma and Antioxidants: Review and Update. Antioxidants. 2020; 9(11):1031. https://doi.org/10.3390/antiox9111031
Chicago/Turabian StyleGarcia-Medina, Jose Javier, Elena Rubio-Velazquez, Maria Dolores Lopez-Bernal, Alejandro Cobo-Martinez, Vicente Zanon-Moreno, Maria Dolores Pinazo-Duran, and Monica del-Rio-Vellosillo. 2020. "Glaucoma and Antioxidants: Review and Update" Antioxidants 9, no. 11: 1031. https://doi.org/10.3390/antiox9111031