Enhanced Oxidative Stress and Other Potential Biomarkers for Retinopathy in Type 2 Diabetics: Beneficial Effects of the Nutraceutic Supplements.

We have studied the global risk of retinopathy in a Mediterranean population of type 2 diabetes mellitus (T2DM) patients, according to clinical, biochemical, and lifestyle biomarkers. The effects of the oral supplementation containing antioxidants/omega 3 fatty acids (A/ω3) were also evaluated. Suitable participants were distributed into two main groups: (1) T2DMG (with retinopathy (+DR) or without retinopathy (-DR)) and (2) controls (CG). Participants were randomly assigned (+A/ω3) or not (-A/ω3) to the oral supplementation with a daily pill of Nutrof Omega (R) for 18 months. Data collected including demographics, anthropometrics, characteristics/lifestyle, ophthalmic examination (best corrected visual acuity, ocular fundus photographs, and retinal thickness as assessed by optical coherence tomography), and blood parameters (glucose, glycosylated hemoglobin, triglycerides, malondialdehyde, and total antioxidant capacity) were registered, integrated, and statistically processed by the SPSS 15.0 program. Finally, 208 participants (130 diabetics (68 +DR/62 -DR) and 78 controls) completed the follow-up. Blood analyses confirmed that the T2DMG+DR patients had significantly higher oxidative stress (p < 0.05), inflammatory (p < 0.05), and vascular (p < 0.001) risk markers than the T2DMG-DR and the CG. Furthermore, the A/ω3 oral supplementation positively changed the baseline parameters, presumptively by inducing metabolic activation and ameliorating the ocular health after 18 months of supplementation.

Ocular Surface and Tear Film Changes in Older Women Working with Computers.

The aim of this work is to investigate changes in the ocular surface (OS) and tear film (TF) by means of questionnaire-based subjective symptoms, TF break-up time, Schirmer test, and TF analysis in women working with computers and to analyze the effects of the oral supplementation with antioxidants/omega 3 fatty acids (A/ω3) in the OS outcomes. Women aged 40-65 years (n = 148) were recruited at the Administrative Offices of Valencia (Spain) and distributed into two age groups, 40-52 years (AGE1; n = 87) and 53-65 years (AGE2; n = 61), and then subdivided according to being (or not) computer users (CUG; NCUG) during the workday. Homogeneous subgroups were randomly assigned (or not) to the daily intake of three pills of A/ω3 for three months. At baseline and at the end of follow-up, personalized interviews and ocular examination were done. Reflex tear samples were collected from the inferior meniscus and processed for a multiplexed particle-based flow cytometry assay to measure proinflammatory molecules. Statistics were performed using the SPSS 15.0 program. The OS pathology was clinically evident in the AGE1-CUG (33%) versus the AGE2-CUG (64%) of women. Significantly higher interleukins-1ß and -6 tear levels were found in the AGE1 versus the AGE2 women employees (P = 0.006 and P = 0.001, resp.), as well as in the CUG versus the NCUG (P = 0.001 and P = 0.000, resp.). Supplementation with A/ω3 positively influenced the OS pathology as manifested by the amelioration of the clinical signs/symptoms related to computer uses. Strategies involving a safe environment and oral micronutrient supplements may be managed within eye-care standards in older women.

A metabolomic approach to dry eye disorders. The role of oral supplements with antioxidants and omega 3 fatty acids.

PURPOSE: We used nuclear magnetic resonance spectroscopy of hydrogen-1 nuclei ((1)H NMR S) to analyze the metabolic profile of reflex tears from patients with dry eye disorders. METHODS: We performed a prospective case-control study involving 90 participants: 55 patients diagnosed with dry eye syndrome (DESG) and 35 healthy subjects (control group, CG). From the DESG, two subgroups were formed: mild DES (n=22) and moderate DES (n=33). Participants were prescribed an oral nutraceutic supplementation containing antioxidants and essential polyunsaturated fatty acids to be taken as three capsules per day for 3 months. Reflex tears (20-30 µl) were collected from the tear meniscus of both eyes of each subject with a microglass pipette. Nuclear magnetic resonance (NMR) spectra were acquired with a standard one-dimensional pulse sequence with water suppression; 256 free induction decays were collected into 64,000 data points with 14 ppm spectral width. RESULTS: Basal tears showed a differential metabolomic profile between groups. Almost 50 metabolites were identified by H cholesterol, N-acetylglucosamine, glutamate, amino-n-butyrate, choline, glucose, and formate were detected before supplementation and choline/acetylcholine after supplementation. The metabolic profile of the tears was statistically different between groups, as well as before and after supplementation. CONCLUSIONS: Our data indicate that DES induces changes in the tear metabolic profile that can be modified with appropriate oral supplementation with antioxidants and essential polyunsaturated fatty acids.

Differential effects of dry eye disorders on metabolomic profile by 1H nuclear magnetic resonance spectroscopy.

We used (1)H NMR spectroscopy to analyze the metabolomic profile of reflex tears from patients with dry eye disorders (DEDs). 90 subjects were divided into 2 groups: (1) patients with DEDs (DEDG; n = 55) and (2) healthy subjects (CG; n = 35). Additionally, the DEDG was subdivided into 2 subgroups based on DED severity: mild-to-moderate and moderate (n = 22 and n = 33, resp.). Personal interviews and systematized ophthalmologic examinations were carried out. Reflex tears (20-30 µL) were collected by gently rubbing in the inferior meniscus of both eyelids with a microglass pipette and stored at -80°C until analysis. NMR spectra were acquired using a standard one-dimensional pulse sequence with water suppression. Data were processed and transferred to MATLAB for further chemometric analysis. Main differences in tear composition between DEDG and CG were found in cholesterol, N-acetylglucosamine, glutamate, creatine, amino-n-butyrate, choline, acetylcholine, arginine, phosphoethanolamine, glucose, and phenylalanine levels. This metabolic fingerprint helped also to discriminate between the three additional subgroups of DEDG. Our results suggest that tear metabolic differences between DEDG and CG identified by NMR could be useful in understanding ocular surface pathogenesis and improving biotherapy.

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.

Ojo Seco: Alternativas terapéutica frente a los lubricantes oculares a propósito de una prueba piloto / Dry eye: Therapeutic altenartives from the eye lubricants on purposea test pilot

Existe relación entre trabajadores expuestos a pantallas de visualización de datos y alteraciones de la superficie ocular, medida por citoquinas/quimioquinas que pueden mejorar con la suplementación de ácidos omega-3 y medidas de promoción de la salud en el lugar de trabajo. La prolongación de la vida laboral y el alto nivel de exposición obligan a intervenir a los Servicios de Prevención de Riesgos Laborales (AU)

There is relationship between workers exposed to data visualization screens and ocular surface alterations, measured by cytokines/chemokines that may benefit from supplementation of omega-3 and measures of health promotion in the workplace. The extension of working life and require high level of exposure to intervene Services Occupational Risk Prevention (AU)

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.

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)-1ß, 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-1ß, IL6, IL8, and vascular endothelial growth factor levels, and between the fluorescein breakup time with IL6 and IL8 levels. However, levels of IL-1ß, 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.

Combined pre- and postnatal ethanol exposure in rats disturbs the myelination of optic axons.

AIMS: To analyse myelination and outgrowth of the optic axons in relation to the neuro-ophthalmological manifestations of ethanol (EtOH) abuse during pregnancy. METHODS: An experimental model of chronic EtOH exposure was developed in rats and their offspring by subjecting the dams to a liquid diet (35% of the daily total calories as either EtOH or maltose-dextrose nutritional controls (Con). Eyeballs and optic nerves were obtained at key developmental stages and processed for morphologic, immunocytochemical and immunoblotting procedures, using alternatively antibodies against myelin basic protein (MBP) or neurofilament (NF) protein, and image analysing. RESULTS: A significant delay in onset of optic axons myelination, as well as a significant reduction in optic nerve size (P < 0.001), optic axons number (P < 0.001), myelinated axons density (P < 0.001), number of myelin lamellae linked to axon diameter (P < 0.001) and optic axon cross-sectional area (P < 0.001) were detected in the global morphometric assessment of the EtOH nerves with respect to the Con. Expression of MBP and NF was noticeably reduced in the EtOH optic nerves when compared with the Con. CONCLUSION: Disturbed myelination of optic axons, caused by EtOH abuse, strongly disrupts the optic nerve development and the establishment of definitive retinal and optic nerve targets, and subsequently the visual patterns.

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.