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Effects of Anthocyanins in Black Currant on Retinal Blood Flow Circulation of Patients with Normal Tension Glaucoma. A Pilot Study

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Purpose: To investigate the effects of anthocyanins in black currant on retinal blood flow circulation of patients with normal tension glaucoma (NTG). Methods: Thirty consecutive patients with NTG were included in this study. They were orally administrated anthocyanins extracted from black currant in tablet form once a day for a 6-month period. Systemic blood pressures. intraocular pressures (IOPs). concentrations of the plasma endothelin-1 (ET-l), blood flows at the neuroretinal rim of the optic nerve head and peripapillary retina. and visual field defects were measured before and just after the administration period. Results: Our study demonstrated that oral administration of anthocyanins tablets significantly increased the blood flows at both neuroretinal rim of the optic nerve head and peripapillary retina (p < 0.05). with no significant changes in mean blood pressures or IOPs. Furthermore. none of the subjects showed progression of their visual field defects. We also demonstrated that the oral administration of anthocyanins tablets significantly increased. and thus normalized the concentrations of plasma ET-1 (p < 0.05). Conclusion: These results suggest that anthocyanins orally administrated might be a safe and valuable choice for neuroprotective treatment of patients with NTG.
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... Seven of the 16 studies used a flavonoid alone (33)(34)(35)(36)(37)(38)(39), and the remaining used mixed supplements (40)(41)(42)(43)(44)(45)(46)(47)(48). The dose of flavonoids ranged from 19 milligrams to 300 milligrams per day. ...
... Various flavonoids were assessed in the studies included in this review. The most commonly tested groups of flavonoids were anthocyanins (35,36,39,45,46,48); other subclasses of flavonoids included flavan-3-ols [e.g., epigallocatechin-gallate (ECGC) and proanthocyanidins] (33,34,42), isoflavones (e.g., puerarin and genistein) (38,43), and flavonols (e.g., rutin and troxerutin) (40,44,47). None of the studies used flavanones. ...
... An extensive number of diagnostic tests have been used in the included studies, such as best-corrected visual acuity (BCVA) assessment, electroretinogram, tonometry, and fundus photography. Seven studies involving 506 participants focused on glaucoma (33,35,36,39,42,46,47), and three clinical trials focused on DR (34,38,43). Two studies, authored by the same group, evaluated the different outcomes associated with cystoid macular edema (40,41). ...
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Background: Emerging studies show that certain plant compounds may reduce the severity of most prevalent ocular abnormalities. The aim of this systematic review and meta-analysis was to assess the effect of dietary flavonoids on major eye disorders. Methods: Eligible studies were identified by searching PubMed, Web of Science, Scopus, and Cochrane Library databases for all articles published up to April 2021. The literature search yielded 1,134 articles, and a total of 16 studies were included in the systematic review. A meta-analysis of 11 intervention trials involving a total of 724 participants was performed. Results: Using a random-effects model, the pooled results revealed an overall significant effect of flavonoids on common ophthalmic disorders (standard mean difference = −0.39; 95% CI: −0.56, −0.21, p < 0.01). Of the subclasses of flavonoids, flavan-3-ols (standard mean difference = −0.62; 95% CI: −1.03, −0.22, p < 0.01), and anthocyanins (standard mean difference = −0.42; 95% CI: −0.63, −0.21, p < 0.01) were the only effective intervention for improving the outcomes of ocular conditions. For several of the other flavonoid subclasses, evidence on efficacy was insufficient. Conclusion: Our findings indicate that flavonoids may improve the clinical manifestations associated with ocular disorders. However, further well-constructed clinical trials are required to confirm these results and examine the effect of flavonoids on eye disorders other than those identified in this review. Systematic Review Registration: PROSPERO, identifier CRD42021247332.
... Recent studies, however, show that the inherent chemical antioxidant properties of fruits is not necessarily a good indicator of their actual health-benefiting properties. Blackcurrant anthocyanins, for example, have also been shown to exhibit health properties independent of their antioxidant capability using both in vitro cell studies (30)(31)(32) and human nutrition studies, whereby consumption of blackcurrant anthocyanin compounds have been reported to support innate immunity (33)(34)(35), improve eye blood flow (36) and augment the adaptive events of exercise (37,38). In this study, we assessed the dose and temporal bioavailability of anthocyanins after consumption of a New Zealand blackcurrant anthocyanin-rich extract (BAE) and apply this knowledge in a pilot trial designed to examine the dose-dependent effect of pre-exercise BAE consumption on recovery from exerciseinduced oxidative stress and the maintenance of circulating neutrophil function. ...
... In our study, the peak plasma anthocyanin bioavailability at 2 h post-consumption was similar in both studies irrespective of the initial blackcurrant extract dose consumed. However, despite the reported anthocyanin bioavailability differences, the findings from our current study and that of others (36,49) demonstrate a close relationship between optimal plasma anthocyanin bioavailability and functional efficacy. ...
... In this pilot study, we found timed consumption of BAE (3.2 mg/kg) prior to exercise attenuated the transient post-exercise decline in circulating neutrophils as well as supported the increase in circulating neutrophils during recovery. Although the underlying mechanism is unknown, it is feasible that the bioavailability of blackcurrant anthocyanins prior to exercise may improve blood flow (36) to support rapid neutrophil influx during recovery (outflux after recovery) and/or maintain the existing neutrophil population through the removal of potential oxidants such as lactic acid (63). Since neutrophils are the first line of defense against microbial infection, it is also important that circulating neutrophils possess and maintain their functional capacity in response to exercise and subsequent recovery. ...
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Aim: To evaluate blackcurrant anthocyanin-rich extract (BAE) consumption on time- and dose-dependent plasma anthocyanin bioavailability and conduct a pilot study to explore the potential effect of BAE in promoting recovery from exercise-induced oxidative stress, and maintenance of circulating neutrophil function. Methods: Time- and dose-dependent blackcurrant anthocyanin bioavailability was assessed using LC-MS in 12 participants over 6 h after the ingestion of a placebo or BAE containing 0.8, 1.6, or 3.2 mg/kg total anthocyanins. In a separate pilot intervention exercise trial, 32 participants consumed either a placebo or 0.8, 1.6, or 3.2 mg/kg BAE (8 individuals per group), and then 1 h later performed a 30 min row at 70% VO2max. Blood was collected during the trial for oxidative, antioxidant, inflammatory, and circulating neutrophil status. Results: Consumption of BAE caused a time- and dose-dependent increase in plasma anthocyanins, peaking at 2 h after ingestion of 3.2 mg/kg BAE (217 ± 69 nM). BAE consumed 1 h prior to a 30 min row had no effect on plasma antioxidant status but hastened the recovery from exercise-induced oxidative stress: By 2 h recovery, consumption of 1.6 mg/kg BAE prior to exercise caused a significant (P < 0.05) 34 and 32% decrease in post-exercise plasma oxidative capacity and protein carbonyl levels, respectively, compared to placebo. BAE consumption prior to exercise dose-dependently attenuated a small, yet significant (P < 0.01) transient 13 ± 2% decline in circulating neutrophils observed in the placebo group immediately post-exercise. Furthermore, the timed consumption of either 1.6 or 3.2 mg/kg BAE attenuated a 17 ± 2.4% (P < 0.05) decline in neutrophil phagocytic capability of opsonised FITC-Escherichia coli observed 6 h post-exercise in the placebo group. Similarly, a dose-dependent increase in neutrophil surface expression of complement receptor-3 complex (CR3, critical for effective phagocytosis of opsonised microbes), was observed 6 h post-exercise in both 1.6 and 3.2 mg/kg BAE intervention groups. Conclusions: Consumption of BAE (>1.6 mg/kg) 1 h prior to exercise facilitated recovery from exercise-induced oxidative stress and preserved circulating neutrophil function. This study provides data to underpin a larger study designed to evaluate the efficacy of timed BAE consumption on post-exercise recovery and innate immunity.
... One uncontrolled intervention study reported no benefit of BCACs on VF among participants with NTG. 97 The highest quality RCT evidence, however, indicates a possible beneficial effect. It was observed that the mean deterioration of MD after 24 months of supplementation was significantly less in the BCACs-treated group compared to placebo (P ¼ 0.039, unpaired t-test). ...
... A pilot uncontrolled study by Ohguro and coworkers showed a significant increase in OBF at both the neuroretinal rim of the optic nerve head and at the peripapillary retina after 6 months of supplementation with 50 mg/day BCACs in NTG. 97 Although no change in ocular perfusion pressure was observed, blood flow at the superior and inferior temporal neuroretinal rim of the optic nerve head and the superior and inferior peripapillary retina increased significantly after supplementation. The results of this pilot study were further confirmed by a longer term RCT by the same group. ...
... Plasma concentrations of endothelin-1 (ET-1) were observed to increase significantly in 30 NTG patients after 6 months of supplementation with BCACs. 97 As there was no control group, these findings are difficult to interpret in isolation. In a follow-up study, serum samples were analyzed for concentrations of ET-1, nitric oxide, advanced oxidation protein products, and antioxidant capacity. ...
Article
Current treatment strategies for glaucoma are limited to halting disease progression and do not restore lost visual function. Intraocular pressure is the main risk factor for glaucoma, and intraocular pressure–lowering treatment remains the mainstay of glaucoma treatment, but even successful intraocular pressure reduction does not stop the progression of glaucoma in all patients. We review the literature to determine whether nutritional interventions intended to prevent or delay the progression of glaucoma could prove to be a valuable addition to the mainstay of glaucoma therapy. A total of 33 intervention trials were included in this review, including 21 randomized controlled trials. These suggest that flavonoids exert a beneficial effect in glaucoma, particularly in terms of improving ocular blood flow and potentially slowing progression of visual field loss. In addition, supplements containing forskolin have consistently demonstrated the capacity to reduce intraocular pressure beyond the levels achieved with traditional therapy alone; however, despite the strong theoretical rationale and initial clinical evidence for the beneficial effect of dietary supplementation as an adjunct therapy for glaucoma, the evidence is not conclusive. More and better quality research is required to evaluate the role of nutritional supplementation in glaucoma.
... I. Ohguri и соавт. [30] выявили нормализацию уровня ЕТ-1 в сыворотке крови и улучшение гемоперфузии глаза у пациентов с глаукомой после длительного (в течение 24 месяцев) перорального употребления 50 мг антоцианозидов в сутки. Наблюдения, сделанные авторами, подтверждают, что антоцианозиды значительно влияют на метаболизм ЕТ-1 благодаря воздействию на рецепторы ЕТ-1 с последующим высвобождением оксида азота, обладающего вазодилатирующим эффектом. ...
... По мнению большинства авторов, антоцианозиды принимают активное участие в регуляции микроциркуляции, которая осуществляется благодаря изменению диаметра микрососудов с участием миогенных, метаболических и других механизмов [12,23,30]. Результирующий эффект действия антоцианозидов складывается из метаболической регуляции кровотока и потоко-зависимой вазодилатации вследствие воздействия на сосудистый эндотелий (рис. ...
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The literature review presents information on positive effects of anthocyanins on functional indices of cardiovascular system, vascular reactivity of main arteries, microcirculation and retrobulbar blood flow. The positive effect of anthocyanins on the reactivity of main arteries was detected using non-invasive ultrasound method for assessment of flow-mediated dilation andendothelial function. Numerous randomised-controlled trials showed the effectiveness of the long-term supplementation with anthocyanins (during 6–24 months) in correction of microcirculation impairment and functional indices of visual system. The increase of plasma endothelin-1 (ET-1) level and the pathological vascular reactivity have been noted in ocular ischemic diseases such as diabetic retinopathy, occlusion of retinal veins and arteries. We registered the normalization of the plasma ET-1 level, significant improvement of blood flow in neuroretinal rim area and peripapillary area of retina without changes in mean indices of intraocular pressure and ocular perfusion pressure in patients with open-angle glaucoma after anthocyanins administration. There was no progression of visual fields defects. The resulting effect of anthocyanins supplementation consists of metabolic regulation of blood flow and flow-dependent vasodilatation due to the influence on vascular endothelium.Anthocyanins also increase the expression of endothelial nitric oxide (NO) synthase, an enzyme that generates powerful endogenous vasodilator NO. Anthocyanins regulate a number of complex immune and inflammatory signaling pathways involved in maintaining vascular functional activity. Positive dynamic of blood flow velocities and normalization of resistance indices in ocular vessels were detected in patients with dry age-related macular degeneration after 2 months anthocyanins supplementation. That indicates the improvement of ocular blood flow circulation and favorable prognosis for retinal dystrophies. The instrumental examination of blood flow in different vascular systems including microcirculation and main arteries are very useful for assessment of the effectiveness of anthocyanin supplementation.
... Ohguro and coworkers conducted a series of clinical trials to assess the possible beneficial effect of BCAC in glaucoma progression. Initially, in a pilot clinical trial, they found that the administration of BCAC to patients with normal-tension glaucoma for six months caused a significant increase in the blood flow at the optic nerve head as well as at peripapillary retina levels; however, no significant IOP or visual field changes were detected 149 . In a subsequent randomized, placebo-controlled trial, the same authors demonstrated that 2-year BCAC supplementation significantly decreased deterioration of visual field mean deviation and increased ocular blood flow of OAG patients compared to placebo-treated ones. ...
Article
Glaucoma is a major ocular neurodegenerative disease characterized by progressive retinal ganglion cells degeneration and sight loss. Current treatment options have been limited to reducing intraocular pressure (IOP), known as the leading risk factor for this disease; however, glaucoma can develop even with low or normal IOP and progress despite controlling IOP values. Lifestyle, dietary habits, and supplementation may influence some of the risk factors and pathophysiological mechanisms underlying glaucoma development and progression; thus, the role of this complementary and alternative medicine in glaucoma has received great interest from both patients and ophthalmologists. We provide a summary of the current evidence concerning the relationship between lifestyle, dietary habits, and effects of supplements on the incidence and progression of glaucoma and their targets and associated mechanisms. The data suggest the existence of a therapeutic potential that needs to be further explored with both preclinical and rigorous clinical studies.
... It's worth noting that anthocyanins intake improves transient myopic shift, dark adaptation and the retinal blood circulation in normal-tension glaucoma patients (Yanamala, 2009;Ohguro, 2007;Nomi, 2019). The Side Effects of Anthocyanins: Anthocyanins toxicity has not been shown in currently published human intervention studies (Wallace and Giusti, 2015). ...
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Anthocyanins are coloured water-soluble pigments representing one of the major subclasses of compounds. They rarely exist in nature as free aglycons, instead, they attach to one or more sugar moieties. Anthocyanins are found within different plant organs; flowers, leaves, fruits, roots, tubers and grains. They appear in different attractive colours depending on their structure, pH, and other factors. These compounds gained a lot of attention in the last few years as food colourants replacing chemical dyes, besides their role in enhancing plant tolerance against many abiotic stresses such as salinity, drought, excessive light, ultraviolet radiation and cold stress. Besides, previous studies demonstrated the importance of anthocyanins in human health and their protective properties against chronic diseases. Hence, this review focuses on anthocyanins as one of the most important pigments having beneficial roles in health for plants and humans.
... Mechanistically, cyanidin-3-glycosides stimulate the regeneration of rhodopsin (57), and delphinidin-3-rutinoside relaxes bovine ciliary smooth muscle by activating endothelin B receptor and the NO/cyclic guanosine-5 -monophosphate pathway (58). Clinical trials have reported endothelium-dependent vasorelaxation induced by blackcurrant leading to the improvement of retinal blood circulation in normaltension glaucoma patients (59,60). Furthermore, blackcurrant intake improved dark adaptation and VDU-induced transient myopic shift in healthy humans (22). ...
Article
Background: With the frequent use of video display units, eye fatigue is becoming more common globally. An alternative nutritional strategy is needed to prevent the aggravation of eye fatigue symptoms. Objectives: The objective was to evaluate the protective effect of a novel botanical combination of lutein ester, zeaxanthin, and extracts of blackcurrant, chrysanthemum, and goji berry on adults with eye fatigue in a randomized, double-blind, placebo-controlled clinical trial. Methods: We randomly allocated 360 participants into 4 groups to receive placebo and 3 doses of our formula (chewable tablets, containing 6 mg, 10 mg, or 14 mg of lutein) once daily for 90 d. Each participant had 3 visits at baseline (V1), 45 d (V2), and 90 d (V3) during the study. Results: Intervention with the formula improved individual scores of eye fatigue symptoms, including eye soreness, blurred vision, dry eye, foreign body sensation, and tearing. Compared with placebo, the formula at all 3 doses significantly decreased the total score of eye fatigue symptoms and increased the visuognosis persistence time at both V2 and V3. According to the Schirmer test, both 10-mg and 14-mg lutein formula groups had improved tear secretion at V3 compared with the placebo. The keratography results indicated that the first tear break-up time, average tear break-up time, and tear meniscus height were significantly increased after formula intervention. The formula at all 3 doses significantly increased the macular pigment optical density at V2 and V3 compared with the placebo, whereas optical coherence tomography showed no significant difference in retinal thickness and retinal volume across all groups at both visits. Conclusions: Our botanical formula improves eye fatigue, dry eye, and macular function without changing the retinal structure, and thus it could serve as an effective nutritional strategy in improving eye fatigue without causing serious side effects.Clinical Trial Registry: chictr.org.cn (ChiCTR1800018987).
... In a clinical study, thirty consecutive hospital visit patients (age range, 51-80; mean age 66.7 ± 6.9 years-old, nine males and 21 females) with normal tension glaucoma (NTG) received 50 mg orally administered BCA once daily for 6 months [63]. Blood flow at the neuroretinal rim of the optic nerve head and peripapillary retina was evaluated using a scanning laser Doppler flow meter both before and after 6 months of administration [64]. ...
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Anthocyanin (AC) is widely used as supplement of eye health in Europe and in East Asia. In this review, I describe AC effects to clarify the mechanism is important in order to understand the effects of AC on vision health. The bioavailability of AC is quite low but, reported as intact form and many kinds of metabolite. And AC passes through the blood-aqueous fluid barrier and blood-retinal barrier. In vitro study, AC had a relaxing effect on ciliary muscle which is important to treat both myopia and glaucoma. And AC stimulate the regeneration of rhodopsin in frog rod outer segment. Furthermore, AC could inhibit the axial length and ocular length elongation in a negative lens-induced chick myopia model. In addition, we summarized clinical studies of AC intake improved dark adaptation and transient myopic shift and the improvement on retinal blood circulation in normal tension glaucoma patients.
... Compared to animal and in vitro research, there are relatively few clinical studies examining anthocyanin effects on human vision, particularly studies that adequately satisfy design criteria, including randomization, blinding, placebo control, and crossover, as previously described (129,130). In normotensive glaucoma patients (n = 30), visual field defects were stabilized, ocular blood flow was improved, and Blueberry health benefits 5 plasma endothelin was normalized after 6 mo of daily intake of black currant anthocyanin (50 mg) (131). Similar benefits were observed in a trial in patients medicated for open-angle glaucoma, who received 25 mg anthocyanin daily for 2 y (132). ...
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Awareness of the human health benefits of blueberries is underpinned by a growing body of positive scientific evidence from human observational and clinical research, plus mechanistic research using animal and in vitro models. Blueberries contain a large number of phytochemicals, including abundant anthocyanin pigments. Of their various phytochemicals, anthocyanins probably make the greatest impact on blueberry health functionality. Epidemiological studies associate regular, moderate intake of blueberries and/or anthocyanins with reduced risk of cardiovascular disease, death, and type 2 diabetes, and with improved weight maintenance and neuroprotection. These findings are supported by biomarker-based evidence from human clinical studies. Among the more important healthful aspects of blueberries are their anti-inflammatory and antioxidant actions and their beneficial effects on vascular and glucoregulatory function. Blueberry phytochemicals may affect gastrointestinal microflora and contribute to host health. These aspects have implications in degenerative diseases and conditions as well as the aging process. More evidence, and particularly human clinical evidence, is needed to better understand the potential for anthocyanin-rich blueberries to benefit public health. However, it is widely agreed that the regular consumption of tasty, ripe blueberries can be unconditionally recommended.
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Background: Several studies have shown effects of anthocyanin on blood pressure, blood glucose, and lipid profile in different conditions, but the results of these studies are controversial. We summarized evidence from randomized clinical trials (RCTs) that investigated the effects of anthocyanin supplementation on cardio-metabolic biomarkers in adults. Methods: The literature searches of MEDLINE and EMBASE for published studies in English was performed up to August 2017. Results were summarized as mean differences (MD) with 95% confidence intervals (CI). Effect sizes of eligible studies were pooled using random-effects models (the DerSimonian-Laird estimator). Heterogeneity among studies was evaluated by the Cochrane Q test. Results: Of 5370 papers, 19 RCTs met inclusion criteria. There was no significant effect of anthocyanin supplementation on weight, waist circumference (WC), body mass index (BMI), systolic and diastolic blood pressure (SBP and DBP). Our results indicated that anthocyanin supplementation had no significant effects on HbA1c (MD: -0.32; 95% CI = -0.64, 0.00; p = 0.050) with no heterogeneity (I2 = 0.0%, p = 0.966, no significant heterogeneity), however anthocyanin supplementation had significant effect on HOMA-IR (MD: -0.21; 95% CI = -0.36, -0.07; p = 0.004) (I2 = 37.9%, p = 0.200, no significant heterogeneity) in adults. Intake of anthocyanin had no significant effects on FBS (MD: 0.25; 95% CI = -5.70, 6.21; p = 0.933) and serum insulin (MD: 0.09; 95% CI = -0.92, 1.11; p = 0.860) with high heterogeneity for these variables (p = 0.000, and I2 = 83.5%) and (p = 0.098, and I2 = 52.4%), respectively. Anthocyanin supplementation had significant effects on total cholesterol (TC) and low density lipoprotein (LDL) for more than 300 mg/day intervention for more than 12 weeks. The dose and duration of supplementation were the potential sources of heterogeneity among most of the trials. Conclusion: The results demonstrate that supplementation with anthocyanin have beneficial effect on HOMA-IR in adults.
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PURPOSE: To investigate the association between control of intraocular pressure after surgical intervention for glaucoma and visual field deterioration. METHODS: In the Advanced Glaucoma Intervention Study, eyes were randomly assigned to one of two sequences of glaucoma surgery, one beginning with argon laser trabeculoplasty and the other trabeculectomy. In the present article we examine the relationship between intraocular pressure and progression of visual field damage over 6 or more years of follow-up. In the first analysis, designated Predictive Analysis, we categorize 738 eyes into three groups based on intraocular pressure determinations over the first three 6-month follow-up visits. In the second analysis, designated Associative Analysis, we categorize 586 eyes into four groups based on the percent of B-month visits over the first 6 follow-up years in which eyes presented with intraocular pressure less than 18 mm Hg, The outcome measure in both analyses is change from baseline in follow-up visual field defect score (range, 0 to 20 units). RESULTS: In the Predictive Analysis, eyes with early average intraocular pressure greater than 17.5 mm Hg had an estimated worsening during subsequent follow-up that was 1 unit of visual field defect score greater than eyes with average intraocular pressure less than 14 mm Hg (P = .002). This amount of worsening was greater at 7 years (1.89 units; P < .001) than at 2 years (0.64 units; P = .071), In the Associative Analysis, eyes with 100% of visits with intraocular pressure less than 18 mm Hg over 6 years had mean changes from baseline in visual field defect score close to zero during follow-up, whereas eyes with less than 50% of visits with intraocular pressure less than 18 mm Hg had an estimated worsening over follow-up of 0.63 units of visual field defect score (P = .083). This amount of worsening was greater at 7 years (1.93 units; P < .001) than at 2 years (0.25 units; P = .572). CONCLUSIONS: In both analyses low intraocular pressure is associated with reduced progression of visual field defect, supporting evidence from earlier studies of a protective role for low intraocular pressure in visual field deterioration.
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PURPOSE. To assess vascular endothelial function in patients with normal pressure glaucoma using forearm blood flow responses to intra-arterial infusions of endothelial-dependent and -independent vasoactive agents. METHODS. Eight patients with newly diagnosed and untreated normal pressure glaucoma and eight healthy age- and sex-matched control volunteers underwent measurement of forearm blood flow using venous occlusion plethysmography. Blood flow was assessed in response to Incremental doses of sodium nitroprusside (an endothelial-independent vasodilator), acetylcholine (an endothelial-dependent vasodilator) and the vasoconstrictor N-G-monomethyl-L-arginine (an inhibitor of nitric oxide synthase). RESULTS. Sodium nitroprusside caused a dose-related increase in forearm blood flow in patients;Ind controls. Glaucoma patients appeared to have an increased vasodilatory response, but this was not significant (P = 0.23). Acetylcholine also induced vasodilatation in both groups, but the response was significantly reduced in the glaucoma group (P = 0.04). N-G-monomethyl-L-arginine induced a similar degree of vasoconstriction in both groups (P = 0.76). CONCLUSIONS. This study has shown an impairment of peripheral endothelium-mediated vasodilatation in normal pressure glaucoma. These findings would support the concept of a generalized vascular endothelial dysfunction in patients with this condition.
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Purpose: To study of contribution of plasma endothelin-1 (ET-0) concentration to pathogenesis of glaucomatous optic neuropathy. Subjects and Methods: We examined plasma ET-1 concentrations in 102 patients with normal tension glaucoma (NTG), 90 patients with primary open-angle glaucoma (POAG) and 78 age-matched non-glaucomatous subjects (CONT). In addition, the relationship between the plasma ET-1 concentrations and glaucoma stages were also studied. Results: Plasma ET-1 concentrations of patients with NTG (3.34±1.27 pg/ml, P<0.01) and POAG (3.80±1.40 pg/ml, P<0.05) were significantly lower than those of CONT (4.39+1.34 pg/ml). No relation was observed between these plasma ET-1 concentrations and glaucoma stages in NTG and POAG. Conclusions: These results indicate that plasma ET-1 may be involved in the pathogenesis of glaucomatous optic neuropathy.
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Background: Overproduction of endothelin-1 (ET-1) and nitric oxide (NO) in the retina is demonstrated in experimental diabetic animals. To clarify the possible involvement of ET-1 and NO in the pathogenesis of diabetic retinopathy, the authors examined the vitreous levels of these principal endothelium-derived vasoactive substances in patients with proliferative diabetic retinopathy (PDR). Methods: Vitreous fluid was taken from patients with PDR (ET-1, n = 12; NO, n = 12) and from patients with macular holes as controls (ET-1, n = 10; NO, n = 10) at vitreous surgery. Endothelin-1 and NO metabolites were measured by radioimmunoassay and high-performance liquid chromatography based on the Griess method, respectively. Results: Endothelin-1 levels (mean ± SE) were 21.5 ± 1.7 pg/mL in the vitreous of patients with PDR and 16.7 ± 0.7 pg/mL in the vitreous of patients with macular hole. There was a significant difference between patients with PDR and controls (P = 0.009, Mann-Whitney). Nitrate (NO3) was 49.8 ± 5.0 μmol/L in patients with PDR and 24.2 ± 2.8 μmol/L in patients with macula hole; it was also significantly elevated in patients with PDR (P = 0.004, Mann-Whitney), whereas nitrite (NO2) was not detected in this study. Conclusion: These results indicate that ET-1 and NO may be related in the pathogenesis of PDR.
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We have investigated the localisation of endothelin-1 (ET-1) mRNA and ET-1-like immunoreactivity in retina and anterior portion of optic nerve from human and porcine eyes. In situ hybridisation method revealed expression of ET-1 mRNA mainly in the innermost layers of the retinas, in the retinal pigment epithelium cells as well as in the astrocytes of the optic nerve. Immunohistochemical studies showed that ET-1-like immunoreactivity appeared in the same regions where ET-1 mRNA was expressed as well as in the inner nuclear layer and in the inner segments of photoreceptors. In the nerve fibre and ganglion cell layers, astrocytes expressed both glial fibrillary acidic protein and ET-1 proteins suggesting that these cells may secrete ET-1. Expression of ETA and ETB receptors in human retina were demonstrated by reverse transcription-polymerase chain reaction. Our results demonstrated expression of ET-1 in glial, neural and vascular components of retina and optic nerve from human and porcine eyes.
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Thesis--University of Tsukuba, D.M.S.(A), no. 592, 1988. 9. 30 Offprint. Originally published in: Nature, v. 332, no. 6163, pp. 411-415, 1988 Joint authors: Hiroki Kurihara ... et al Includes supplementary treatises
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The typical morphological and consequent functional damage caused by disease entities covered by the term ‘glaucoma’ is the result of inadequate circulation to the optic nerve fibres, predominantly in the papillary region, as a result of elevated intraocular pressure. The aim of this study is classification of different forms of glaucoma on the basis of blood flow parameters. Physiological and pathophysiological aspects of ocular blood flow and of microcirculation and hemorrheology will be considered and the significance of ocular vasospasm in low-tension glaucoma discussed. The frequent occurrence of vasospasm in the nailfold capillaries and of visual field deterioration after a coldwater test demonstrates that vasospasm is an expression of different underlying phenomena. Our results show that, in patients with ocular vasospasm, treatment with a calcium antagonist brings about a clear reversal of their visual field defects.
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A prospective study was conducted to evaluate the effects of Ca2(+)-antagonist on the visual field in low-tension glaucoma (LTG). Twenty-five consecutive patients (50 eyes) with LTG received nifedipine at 30 mg/day per os for 6 months. Visual field was tested with an Octopus 201 (program G1) prior to and each month during the period of nifedipine administration. In addition to tonometry and the measurements of systemic blood pressure and pulse rate, the reactivity of peripheral vessels was estimated by determining the response of skin temperature of a finger to cold water (4 degrees C). Twelve eyes (six patients) showed a constant improvement of visual field as expressed by an increase in mean sensitivity (MS). Canonical discriminant analysis demonstrated that the visual field is likely to improve with systemic nifedipine in patients who are young, have a higher initial MS and lower intraocular pressure, and have less decrease in diastolic blood pressure with the nifedipine administration and better cold recovery of skin temperature after their hand is soaked in cold water.
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1829 photographs of optic discs taken during routine examination and follow-up of 320 glaucoma patients and 169 cases of ocular hypertension were examined for the presence of haemorrhages on the disc. As expected, the observed incidence of disc haemorrhages rose with increase in the number of occasions on which the patient was photographed. It was concluded that at least one-third of glaucoma patients show a disc haemorrhage at one time or another. Disc haemorrhages were seen more often in patients with established glaucoma than in those with ocular hypertension. In patients with chronic simple glaucoma eyes with full fields and low cup: disc ratios showed haemorrhages less often than eyes with field defects and more advanced damage to the optic disc, but apart from this there was no marked tendency for haemorrhages to occur at a particular stage of the disease. Haemorrhages were more frequent in low-tension than in chronic simple glaucoma, but this was probably only part of a more general variation which was revealed when eyes were graded according to the maximum pressures ever recorded, there being a very significant trend in which more haemorrhages were found in eyes with lower than with higher intraocular pressures over the range from 10 to 60 mmHg.