Vicente Zanon-Moreno

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.

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.

Dietary Marine ω-3 Fatty Acids and Incident Sight-Threatening Retinopathy in Middle-Aged and Older Individuals With Type 2 Diabetes: Prospective Investigation From the PREDIMED Trial

Importance Diabetic retinopathy (DR) is a devastating complication of individuals with type 2 diabetes mellitus. The retina is rich in long-chain ω-3 polyunsaturated fatty acids (LCω3PUFAs), which are substrate for oxylipins with anti-inflammatory and antiangiogenic properties. Experimental models support dietary LCω3PUFA protection against DR, but clinical data are lacking. Objective To determine whether LCω3PUFA intake relates to a decreased incidence of sight-threatening DR in individuals with type 2 diabetes older than 55 years. Design, Setting, and Participants In late 2015, we conceived a prospective study within the randomized clinical trial Prevención con Dieta Mediterránea (PREDIMED), testing Mediterranean diets supplemented with extra virgin olive oil or nuts vs a control diet for primary cardiovascular prevention. The trial was conducted in primary health care centers in Spain. From 2003 to 2009, 3614 individuals aged 55 to 80 years with a previous diagnosis of type 2 diabetes were recruited. Full data were available for 3482 participants (48% men; mean age 67 years). Exposures Meeting the dietary LCω3PUFA recommendation of at least 500 mg/d for primary cardiovascular prevention, as assessed by a validated food-frequency questionnaire. Main Outcomes and Measures The main outcome was incident DR requiring laser photocoagulation, vitrectomy, and/or antiangiogenic therapy confirmed by an external adjudication committee. Results Of the 3482 participants, 48% were men and the mean age was 67 years. A total of 2611 participants (75%) met target LCω3PUFA recommendation. During a median follow-up of 6 years, we documented 69 new events. After adjusting for age, sex, intervention group, and lifestyle and clinical variables, participants meeting the LCω3PUFA recommendation at baseline (≥500 mg/d) compared with those not fulfilling this recommendation (<500 mg/d) showed a 48% relatively reduced risk of incident sight-threatening DR, with a hazard ratio of 0.52 (95% CI, 0.31-0.88; P = .001). This association was slightly stronger for yearly updated LCω3PUFA intake (relative risk, 0.48; 95% CI, 0.28-0.82; P = .007). Conclusions and Relevance In middle-aged and older individuals with type 2 diabetes, intake of at least 500 mg/d of dietary LCω3PUFA, easily achievable with 2 weekly servings of oily fish, is associated with a decreased risk of sight-threatening DR. Our results concur with findings from experimental models and the current model of DR pathogenesis. Trial Registration clinicaltrials.gov Identifier: http://www.controlled-trials.com/ISRCTN35739639.

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.

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.

Eclectic Ocular Comorbidities and Systemic Diseases with Eye Involvement: A Review

Coexistence of several ocular diseases is more frequent than suspected. In spite of the refractive errors, one or more of the following can be detected simultaneously: glaucoma, cataracts, uveitis, age-related macular degeneration, and dry eyes. In addition, as people age, ocular comorbidities are much more usually seen. Specific diseases are openly acknowledged to affect the eyes and vision, such as diabetes mellitus, hypertension blood pressure, arthritis, hyperthyroidism, neurodegenerative disorders, hematologic malignancies, and/or systemic infections. Recent advances in early diagnosis and therapy of the ophthalmic pathologies have reinforced patient options to prevent visual impairment and blindness. Because of this, it is essential not to overlook sight-threatening conditions such as the ocular comorbidities and/or the eye involvement in the context of systemic disorders. Moreover, the important role of the multidisciplinary cooperation to improve and sustain management of patients affected with eclectic ocular comorbidities and/or systemic disorders with eye repercussion is specifically addressed. This review intends to shed light on these topics to help in making opportune diagnosis and appropriately managing the affected patients.

Thyroid hormone deficiency disrupts rat eye neurodevelopment.

Clinical and experimental studies have highlighted the role played by thyroid hormones (TH) in neural and neuro-sensorial development. However, knowledge on TH mechanisms on the developing visual system is still incomplete. To uncover TH actions on the eyes and vision we carried out a microscopical study on the role of TH in the developing retina and optic nerve, in a rat model of controlled TH deficiency (THD). Morphometric and stereological analyses of the retina and optic nerve showed a reduction in the volume of the eye (p<0.001) and optic nerve cross-sectional area (p<0.001), and thinning of the retinal layers (p<0.001). Glial development and myelination was significantly delayed in the THD optic nerves (p<0.001), as compared to controls. The data indicate that TH play an essential role in neuro-retinogenesis. Substitutive TH therapy in critical periods, should be considered in hypothyroidism-related eye disorders as well as neurodegenerative retinal processes.