Maria Dolores Pinazo-Duran

Oxidative stress in primary open-angle glaucoma.

PurposeTo analyze oxidative stress in primary open-angle glaucoma (POAG). Material and MethodsA case-control study including 90 eyes of 90 patients who needed antiglaucomatous surgery in the course of POAG (glaucoma group, n=50) and from patients who were operated of nonpathologic cataracts (cataract group, n=40). Free radical formation via lipid peroxidation by malondialdehyde-thiobarbituric acid reactive substances (MDA-TBARS) test and total antioxidant status in the aqueous humor samples of both groups were determined. Statistical analyses were carried out in relation to MDA-TBARS and total antioxidant status and their correlations with glaucoma risk factors. ResultsSignificantly higher MDA-TBARS were detected in the POAG with respect to the comparative group of cataract subjects (P<0.001). Antioxidant activity was significantly lower in the POAG than in the cataract group (P<0.001). ConclusionsAqueous humor samples may be used for determining oxidative and antioxidant status in pathologic processes. Glaucomatous eyes had a significant increase in oxidative status and decreased antioxidant activity in the aqueous humor than the cataract eyes. Oxidative stress may play a pathogenical role in the POAG.

Effects of a nutraceutical formulation based on the combination of antioxidants and ω-3 essential fatty acids in the expression of inflammation and immune response mediators in tears from patients with dry eye disorders

Background Women, and those older than 65 years of age, are particularly susceptible to dry eye disorders (DEDs). Inflammation is clearly involved in the pathogenesis of DEDs, and there is mounting evidence on the antioxidant and antiinflammatory properties of essential polyunsaturated fatty acids (EPUFAs). Objective To analyze whether a combined formulation of antioxidants and long-chain EPUFAs may improve the evolution of DEDs. Methods We used a prospective study to address the relationship between risk factors, clinical outcomes, and expression levels of inflammation and immune response (IIR) mediators in human reflex tear samples. Participants included: (1) patients diagnosed with nonsevere DEDs (DED group [DEDG]); and (2) healthy controls (control group [CG]). Participants were randomly assigned to homogeneous subgroups according to daily oral intake (+S) or not (−NS) of antioxidants and long-chain EPUFAs for 3 months. After an interview and a systematized ophthalmic examination, reflex tears were collected simultaneously from both eyes; samples were later subjected to a multiplexed particle-based flow cytometry assay. A specific set of IIR mediators was analyzed. All data were statistically processed through the SPSS 15.0 software program. Results Significantly higher expressions of interleukin (IL)-1β, IL6, and IL10 and significantly lower vascular endothelial growth factor expressions were found in the DEDG as compared to the CG. In the DEDG, significant negative correlations were detected between the Schirmer test and IL-1β, IL6, IL8, and vascular endothelial growth factor levels, and between the fluorescein breakup time with IL6 and IL8 levels. However, levels of IL-1β, IL6, and IL10 in tears were significantly lower in the DEDG+S versus the DEDG−NS and in the CG+S versus the CG−NS. Subjective symptoms of dry eye significantly improved in the DEDG+S versus the DEDG−NS. Conclusion IIR mediators showed different expression patterns in DED patients, and these patterns changed in response to a combined formulation of antioxidant and EPUFAs supplementation. Our findings may be considered for future protocols integrating clinical/biochemical data to help manage DED patients.

Evaluation of presumptive biomarkers of oxidative stress, immune response and apoptosis in primary open-angle glaucoma.

There is growing interest on the correlation among oxidative stress, inflammation, apoptosis and primary open-angle glaucoma initiation and progression. Reactive oxygen species are formed in the eyes following a wide variety of stressors, and are largely implicated in glaucoma pathogenesis. Immune-inflammatory response mediators have recently become a target of ophthalmologic concern, including glaucoma. Much attention has been derived to the role of specific pro and anti-apoptotic molecules in glaucoma. This article reviews the early evidence suggesting that reactive oxygen species, immune inflammatory response mediators, and apoptogenic molecules are engaged in glaucoma disease. Moreover, further research concerning the functions, effectors and signaling pathways of the above molecules and their interactions, may lead to specifically develop targeted screening tools based on presumptive biomarkers and surrogate endpoints against primary open-angle glaucoma progression and blindness.

A 5-year follow-up of antioxidant supplementation in type 2 diabetic retinopathy.

Purpose This study was designed to evaluate the effect of antioxidant supplementation on diabetic retinopathy (DR) over a 5-year follow-up period. To our knowledge, this is the first such clinical trial performed. Methods We recruited 105 type 2 diabetic patients with nonproliferative DR. A complete ophthalmic checkup and a plasma determination of oxidative (malonyldialdehyde [MDA]) and antioxidant parameters (total antioxidant status [TAS]) were obtained as the baseline. One part of the cohort was randomly assigned to oral antioxidant supplementation at nutritional doses. The same examinations were performed with 97 diabetic patients who completed the 5-year follow-up period. The best-corrected visual acuity, DR score, MDA, and TAS values were compared at the beginning and the end of the follow-up. Results Best-corrected visual acuity did not change during the follow-up, irrespective of supplementation. However, the retinopathy stage showed a retardation of progression in the subgroup with supplementation, but worsened in the subgroup with no antioxidant supplementation. Furthermore, the antioxidant supplementation group maintained its antioxidant plasma status levels, which was related to decreased oxidative plasma activity. Conclusions Oral antioxidant supplementation could be a useful adjunctive long-term therapy in the treatment of nonproliferative DR.

Oxidative stress and its downstream signaling in aging eyes

Background Oxidative stress (OS) and its biomarkers are the biochemical end point of the imbalance between reactive oxygen species (ROS) production and the ability of the antioxidant (AOX) biological systems to fight against oxidative injury. Objective We reviewed the role of OS and its downstream signaling in aging eyes. Methods A search of the literature and current knowledge on the physiological and pathological mechanisms of OS were revisited in relation to the eyes and the aging process. Most prevalent ocular diseases have been analyzed herein in relation to OS and nutraceutic supplements, such as dry-eye disorders, glaucoma, age-related macular degeneration, and diabetic retinopathy. Results Clinical, biochemical, and molecular data from anterior and posterior eye segment diseases point to OS as the common pathogenic mechanism in the majority of these ocular disorders, many of which are pathologies causing visual impairment, blindness, and subsequent loss of life quality. Studies with nutraceutic supplements in aging eye-related pathologies have also been reviewed. Conclusion OS, nutritional status, and nutraceutic supplements have to be considered within the standards of care of older ophthalmologic patients. OS biomarkers and surrogate end points may help in managing the aging population with ocular diseases.

Patients undergoing long-term treatment with antihypertensive eye drops responded positively with respect to their ocular surface disorder to oral supplementation with antioxidants and essential fatty acids

Background Glaucoma and dry eye disorders (DEDs) are frequent comorbidities. The antioxidant and anti-inflammatory properties of essential polyunsaturated fatty acids have been extensively studied in relation to eye diseases. Objective Our objective was to determine the effects of oral supplementation with a combined formulation of antioxidants and essential polyunsaturated fatty acids on expression of cytokines and chemokines in tears from patients with DEDs or primary open-angle glaucoma (POAG). Methods Participants (n = 97) were distributed into three groups: (1) individuals with nonsevere DEDs (DEDG), (2) individuals with nonadvanced POAG (POAGG), and (3) healthy controls. These groups were randomized into two subgroups: one received a daily antioxidant and essential polyunsaturated fatty acid supplement (two pills) for 3 months (+S), and the other did not (−NS). Participants were interviewed and ophthalmologically examined. Concentrations of specific cytokines and chemokines in reflex tears were determined by multiplexed particle-based flow cytometry. The data were analyzed statistically (SPSS version 15.0). Results Comparison of the results from the DEDG and POAGG patients showed significant differences in tear expression of granulocyte-macrophage colony-stimulating factor (P = 0.008), tumor necrosis factor α (P = 0.005), vascular endothelial growth factor (P = 0.038), interleukin-4 (P = 0.030), and interleukin-6 (P = 0.044). The main signs and symptoms of dry eyes such as dryness, burning, photophobia, eye heaviness, and blurred vision, as well as positive changes in eyelashes, hair, nails and skin, were significantly improved in DEDG +S and POAGG +S patients relative to unsupplemented patients. Conclusion Inflammation biomarkers were differentially expressed in glaucomatous tears, but the differences changed upon antioxidant/essential polyunsaturated fatty acid supplementation. Chronic instillation of antihypertensive eye drops must be considered for integrating protocols to glaucoma standards of care.

A two-year follow-up of oral antioxidant supplementation in primary open-angle glaucoma: an open-label, randomized, controlled trial.

To evaluate the effect of oral antioxidant supplementation (OAS) on primary open‐angle glaucoma (POAG) over a 2‐year follow‐up period.

Oxidative stress response in the adult rat retina and plasma after repeated administration of methamphetamine

Methamphetamine (MA) is a psychostimulant that target the sensory systems, with the neurosensory retina having been shown to be affected. In the brain, MA-related toxicity can be linked to oxidative stress; the same relationship has yet to be established for the retina. The aim of this study, therefore, was to evaluate the effects of repeated exposure to MA on oxidative stress parameters in the rat retina. Oxidative stress parameters in the blood plasma were also assessed. Male Wistar rats were given 5mg/kg MA every 2h for a period of 6h (i.e., 4 injections) daily between postnatal day (PND) 91 and 100. Evolution of body weight was registered. Rats were sacrificed at PND 110. Blood plasma was collected and immediately frozen for storage at -70 degrees C. The eyes were enucleated, and the retina and choroids rapidly dissected on ice under dim light also to be stored at -70 degrees C. Lipid peroxidation activity was measured by the thiobarbituric acid (TBA) test. Total antioxidant status, superoxide dismutase (SOD) activity, catalase (Cat) activity, and nitrogen oxides contents were also determined. Lipid peroxidation was significantly higher in the retina and blood plasma of the MA-treated rats. Total antioxidant levels were significantly lower in both retina and blood plasma of the MA-treated rats. The activity of SOD was significantly increased in the retina and blood plasma of MA-treated rats. Catalase activity did not differ between groups in either the retina or the blood plasma. Nitric oxide production was significantly higher in both the retina and blood plasma in the MA-treated animals. The overall findings show that the oxidative stress defence mechanisms in the retina are compromised by MA toxicity. The results are similar to those found in the brain, and, moreover, showed some correlation with the blood plasma.

Metabolomics of the aqueous humor in the rat glaucoma model induced by a series of intracamerular sodium hyaluronate injection

Glaucoma models are helpful to study disease characteristics and to design new therapeutic options. Metabolomic profiling approach have been used to elucidating the molecular characteristics of the aqueous humor. Juvenile male Wistar rats experimental (n = 15) and controls (n = 6) were used for these studies. Experimental rats received weekly intracamerular injection of 25 µl of sodium hyaluronate in the left eye and sterile saline solution in the right eye, consecutively for ten weeks. Rats were subjected to anterior/posterior eye segment examinations, intraocular pressure (IOP), and flash electroretinograms (ERG). The aqueous humor was collected at endpoints and analyzed by Nuclear Magnetic Resonance. Elevated IOP and significant reduction of a, b waves and amplitude of oscillatory potential was observed in the left eyes compared to control eyes. The aqueous humor metabolomic profile from control and the experimental eyes were compared. Concentrations of metabolites (amino acids, lipids and carbohydrates) significantly changed after the sodium hyaluronate injections series, compared to the sham-operated eyes. Metabolic changes in the hypertensive eyes correlated with the impaired retinal function. Observed metabolomic changes in aqueous humor in hypertensive state may play a significant role in glaucoma pathogenesis.

Antioxidant status modifications by topical administration of dorzolamide in primary open-angle glaucoma.

Purpose This study deals with the role of the topical administration of dorzolamide eyedrops on the oxidative/antioxidant status of aqueous humor in patients with primary openangle glaucoma (POAG). Methods A case-control study including 130 patients distributed into three groups was carried out: 1) patients with POAG without dorzolamide instillation administration (GG; n=34); 2) patients with POAG with dorzolamide (DG; n=36); and 3) subjects with cataracts (comparative group, CG; n=60). Oxidative activity was measured in the aqueous humor by malondialdehyde determination by the thiobarbituric acid reactive substances assay. Antioxidant status was assessed in the aqueous humor samples by measuring the superoxide dismutase activity and the total antioxidant status. Results Oxidative activity was significantly higher in both glaucoma groups than in the cataracts group (GG vs CG, p=3.68 E-34; DG vs CG, p=5.11 E-45), and was significantly higher in GG than in DG (p=0.0034). SOD activity was significantly higher in both glaucoma groups than in the cataracts group (GG vs CG, p=1.08 E-14; DG vs CG, p=3.70 E-22), and was significantly higher in GG than in DG (p=0.018). Finally, total antioxidant status was significantly decreased in both glaucoma groups compared with the cataracts group (GG vs CG, p=2.51 E-12; DG vs CG, p=5.06 E-05), and was more significantly decreased in GG than in DG (p=9.23 E-07). Conclusions Topical administration of dorzolamide colirium diminishes oxidative stress in patients with glaucoma.