Glutathione and a Pool of Metabolites Partly Related to Oxidative Stress Are Associated with Low and High Myopia in an Altered Bioenergetic Environment.

Oxidative stress forms part of the molecular basis contributing to the development and manifestation of myopia, a refractive error with associated pathology that is increasingly prevalent worldwide and that subsequently leads to an upsurge in degenerative visual impairment due to conditions that are especially associated with high myopia. The purpose of our study was to examine the interrelation of potential oxidative-stress-related metabolites found in the aqueous humor of high-myopic, low-myopic, and non-myopic patients within a clinical study. We conducted a cross-sectional study, selecting two sets of patients undergoing cataract surgery. The first set, which was used to analyze metabolites through an NMR assay, comprised 116 patients. A total of 59 metabolites were assigned and quantified. The PLS-DA score plot clearly showed a separation with minimal overlap between the HM and control samples. The PLS-DA model allowed us to determine 31 major metabolite differences in the aqueous humor of the study groups. Complementary statistical analysis of the data allowed us to determine six metabolites that presented significant differences among the experimental groups (p < 005). A significant number of these metabolites were discovered to have a direct or indirect connection to oxidative stress linked with conditions of myopic eyes. Notably, we identified metabolites associated with bioenergetic pathways and metabolites that have undergone methylation, along with choline and its derivatives. The second set consisted of 73 patients who underwent a glutathione assay. Here, we showed significant variations in both reduced and oxidized glutathione in aqueous humor among all patient groups (p < 0.01) for the first time. Axial length, refractive status, and complete ophthalmologic examination were also recorded, and interrelations among metabolic and clinical parameters were evaluated.

High Myopia and the Complement System: Factor H in Myopic Maculopathy.

High myopia (HM) is both a medical problem and refractive error of the eye owing to excessive eyeball length, which progressively makes eye tissue atrophic, and is one of the main causes for diminishing visual acuity in developed countries. Despite its high prevalence and many genetic and proteomic studies, no molecular pattern exists that explain the degenerative process underlying HM, which predisposes patients to other diseases like glaucoma, cataracts, retinal detachment and chorioretinal atrophy that affect the macular area. To determine the relation between complement Factors H (CFH) and D (CFD) and the maculopathy of patients with degenerative myopia, we studied aqueous humor samples that were collected by aspiration from 122 patients during cataract surgery. Eyes were classified according to eyeball axial length as high myopia (axial length > 26 mm), low myopia (axial length 23.5-25.9 mm) and control (axial length ˂ 23.4 mm). The degree of maculopathy was classified according to fundus oculi findings following IMI's classification. Subfoveal choroid thickness was measured by optical coherence tomography. CFH and CFD measurements were taken by ELISA. CFH levels were significantly high in the high myopia group vs. the low myopia and control groups (p ˂ 0.05). Significantly high CFH values were found in those eyes with choroid atrophy and neovascularization (p ˂ 0.05). In parallel, the CFH concentration correlated inversely with choroid thickness (R = -0.624). CFD levels did not correlate with maculopathy. All the obtained data seem to suggest that CFH plays a key role in myopic pathology.

Lipid Peroxidation in Subretinal Fluid: Some Light on the Prognosis Factors.

The aim of this study was to identify a relation between the clinical characteristics and differences in lipid peroxidation in the subretinal fluid (SRF) of rhegmatogenous retinal detached patients by malondialdehyde (MDA) quantification. We collected 65 SRF samples from consecutive patients during scleral buckling surgery in rhegmatogenous retinal detachment (RRD) eyes. In addition to a complete ophthalmic evaluation, we studied the refractive status, evolution time, and the number of detached retinal quadrants to establish the extension of RRD. We studied the clinical aspects and oxidative stress and compared the characteristics among groups. We found that neither the evolution time of RRD nor the patients' age correlated with the MDA concentration in the SRF. The MDA and the protein content of the SRF increased in the patients with high myopia and with more extended RRD. Our results suggest that oxidative imbalance was important in more extended retinal detachment (RD) and in myopic eyes and should be taken into account in the managing of these cases.

Role of Oral Antioxidant Supplementation in the Current Management of Diabetic Retinopathy.

Oxidative stress has been postulated as an underlying pathophysiologic mechanism of diabetic retinopathy (DR), the main cause of avoidable blindness in working-aged people. This review addressed the current daily clinical practice of DR and the role of antioxidants in this practice. A systematic review of the studies on antioxidant supplementation in DR patients was presented. Fifteen studies accomplished the inclusion criteria. The analysis of these studies concluded that antioxidant supplementation has a IIB level of recommendation in adult Type 1 and Type 2 diabetes mellitus subjects without retinopathy or mild-to-moderate nonproliferative DR without diabetic macular oedema as a complementary therapy together with standard medical care.

PRPH2-Related Retinal Diseases: Broadening the Clinical Spectrum and Describing a New Mutation.

Over 175 pathogenic mutations in the Peripherin-2 (PRPH2) gene are linked to various retinal diseases. We report the phenotype and genotype of eight families (24 patients) with retinal diseases associated with seven distinct PRPH2 gene mutations. We identified a new mutation, c.824_828+3delinsCATTTGGGCTCCTCATTTGG, in a patient with adult-onset vitelliform macular dystrophy (AVMD). One family with the p.Arg46Ter mutation presented with the already described AVMD phenotype, but another family presented with the same mutation and two heterozygous pathogenic mutations (p.Leu2027Phe and p.Gly1977Ser) in the ATP Binding Cassette Subfamily A Member 4 (ABCA4) gene that cause extensive chorioretinal atrophy (ECA), which could be a blended phenotype. The p.Lys154del PRPH2 gene mutation associated with the p.Arg2030Glu mutation in the ABCA4 gene was found in a patient with multifocal pattern dystrophy simulating fundus flavimaculatus (PDsFF), for whom we considered ABCA4 as a possible modifying gene. The mutation p.Gly167Ser was already known to cause pattern dystrophy, but we also found ECA, PDsFF, and autosomal-dominant retinitis pigmentosa (ADRP) as possible phenotypes. Finally, we identified the mutation p.Arg195Leu in a large family with common ancestry, which previously was described to cause central areolar choroidal dystrophy (CACD), but we also found ADRP and observed that it caused ECA more frequently than CACD in this family.

Imbalance Between Oxidative Stress and Growth Factors in Human High Myopia.

Myopia is one of the commonest eye pathologies that could affect 2.56 billion people by 2020. Today high myopia is a leading cause of blindness worldwide due to associated ocular illness. Nevertheless, the cellular bases for these diseases to develop are unclear in many areas. We conducted a prospective study of oxidative stress and growth factors in human myopic and non myopic eyes in an attempt to increase our understanding of the underlying physiopathological conditions to adequately early diagnose, prevent and treat the retina problem that derives from myopia. Aqueous humor samples were obtained from 41 patients being operated for cataracts in our hospital. Axial length, refractive status and complete ophthalmologic examination were recorded. The VEGF and HGF levels were determined by an ELISA kit. Total antioxidant capacity and total nitrites/nitrate levels were established with a lab kit. We show for the first time an increase in the total nitrite levels in high myopia. We also propose for the first time the concurrence of three factors: myopia, oxidative stress, and oxidative stress together with growth factors in the same group of patients. In this way, it would not be accurate to envision high myopia as a type of normal myopia, but one with more diopters or longer axial length.

Bevacizumab Diminishes Inflammation in an Acute Endotoxin-Induced Uveitis Model.

Introduction: Uveitis is an eye disease characterized by inflammation of the uvea and an early and exhaustive diagnosis is essential for its treatment. The aim of our study is to assess the potential toxicity and anti-inflammatory efficacy of Bevacizumab in an experimental uveitis model by subcutaneously injecting lipopolysaccharide into Lewis rats and to clarify its mechanism. Material and Methods: Blood-aqueous barrier integrity was assessed 24 h after endotoxin-induced uveitis (EIU) by analyzing two parameters: cell count and protein concentration in aqueous humors. Histopathology of all eye structures was also studied. Enzyme-linked immunosorbent analyses of the aqueous humor samples were performed in order to calculate the diverse chemokine and cytokine protein levels and oxidative stress-related markers were also evaluated. Results: The aqueous humor's cellular content significantly increased in the group treated with only Bevacizumab, but it had no effect on retina histopathological grading. Nevertheless, the inflammation noted in ocular structures when administering Bevacizumab with endotoxin was mostly prevented since aqueous humor cell content considerably lowered, and concomitantly with a sharp drop in uveal, vitreous, and retina histopathological grading. The values of the multi-faceted cytokine IL-2 also significantly decreased (p < 0.05 vs. endotoxin group), and the protective IL-6 and IL-10 cytokines values rose with related anti-oxidant system recovery (p < 0.05 vs. endotoxin group). Concurrently, some related M1 macrophage chemokines substantially increased, e.g., GRO/KC, a chemokine that also displays any kind of protective role. Conclusion: All these results revealed that 24 h after being administered, Bevacizumab treatment in EIU significantly prevented inflammation in various eye structures and correct results in efficacy vs. toxicity balance were obtained.