Myopia affected approximately 1.6 billion people worldwide in 2000, and it is expected to increase to 2.5 billion by 2020. Although optical problems can be corrected by optics or surgical procedures, normal myopia and high myopia are still an unsolved medical problem. They frequently predispose people who have them to suffer from other eye pathologies: retinal detachment, glaucoma, macular hemorrhage, cataracts, and so on being one of the main causes of visual deterioration and blindness. Genetic and environmental factors have been associated with myopia. Nevertheless, lack of knowledge in the underlying physiopathological molecular mechanisms has not permitted an adequate diagnosis, prevention, or treatment to be found. Nowadays several pieces of evidence indicate that oxidative stress may help explain the altered regulatory pathways in myopia and the appearance of associated eye diseases. On the one hand, oxidative damage associated with hypoxia myopic can alter the neuromodulation that nitric oxide and dopamine have in eye growth. On the other hand, radical superoxide or peroxynitrite production damage retina, vitreous, lens, and so on contributing to the appearance of retinopathies, retinal detachment, cataracts and so on. The objective of this review is to suggest that oxidative stress is one of the key pieces that can help solve this complex eye problem.

Retinitis pigmentosa (RP) is one of the most common clinical subtypes of retinal degeneration (RD), and it is a neurodegenerative disease that could cause complete blindness in humans because it ultimately affects the photoreceptors viability. RP afflicts an estimated 1.5 million patients worldwide. The retina is highly susceptible to oxidative stress which can impair mitochondrial function. Many retina pathologies, such as diabetic retinopathy and secondary cone photoreceptor death in RP, have been related directly or indirectly with mitochondrial dysfunction. The possible role of autophagy in retina and cell differentiation is described and also the implications of autophagy dysregulation in RP. The present review shows the crucial role of autophagy in maintaining the retina homeostasis and possible therapeutic approaches for the treatment of RP.

Aqueous humor is the transparent fluid found in the anterior chamber of the eye that provides the metabolic requirements to the avascular tissues surrounding it. Despite the fact that metabolomics could be a powerful tool in the characterization of this biofluid and in revealing metabolic signatures of common ocular diseases such as myopia, it has never to our knowledge previously been applied in humans. In this research a novel method for the analysis of aqueous humor is presented to show its application in the characterization of this biofluid using CE-MS. The method was extended to a dual platform method (CE-MS and LC-MS) in order to compare samples from patients with different severities of myopia in order to explore the disease from the metabolic phenotype point of view. With this method, a profound knowledge of the metabolites present in human aqueous humor has been obtained: over 40 metabolites were reproducibly and simultaneously identified from a low volume of sample by CE-MS, including among others, a vast number of amino acids and derivatives. When this method was extended to study groups of patients with high or low myopia in both CE-MS and LC-MS, it has been possible to identify over 20 significantly different metabolite and lipid signatures that distinguish patients based on the severity of myopia. Among these, the most notable higher abundant metabolites in high myopia were aminooctanoic acid, arginine, citrulline and sphinganine while features of low myopia were aminoundecanoic acid, dihydro-retinoic acid and cysteinylglycine disulfide. This dual platform approach offered complementarity such that different metabolites were detected in each technique. Together the experiments presented provide a whelm of valuable information about human aqueous humor and myopia, proving the utility of non-targeted metabolomics for the first time in analyzing this type of sample and the metabolic phenotype of this disease.

Uveitis is an inflammatory process that initially starts in the uvea, but can also affect other adjacent eye structures, and is currently the fourth cause of blindness in developed countries. Corticoids are probably the most widespread treatment, but resorting to other immunosuppressive treatments is a frequent practice. Since the implication of different cytokines in uveitis has been well demonstrated, the majority of recent treatments for this disease include inhibitors or antibodies against these. Nevertheless, adequate treatment for each uveitis type entails a difficult therapeutic decision as no clear recommendations are found in the literature, despite the few protocolized clinical assays and many case-control studies done. This review aims to present, in order, the mechanisms and main indications of the most modern immunosuppressive drugs against cytokines.

Resident and infiltrated macrophages play relevant roles in uveitis as effectors of innate immunity and inductors of acquired immunity. They are major effectors of tissue damage in uveitis and are also considered to be potent antigen-presenting cells. In the last few years, experimental animal models of uveitis have enabled us to enhance our understanding of the leading role of macrophages in eye inflammation processes, including macrophage polarization in experimental autoimmune uveoretinitis and the major role of Toll-like receptor 4 in endotoxin-induced uveitis. This improved knowledge should guide advantageous iterative research to establish mechanisms and possible therapeutic targets for human uveitis resolution.

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.

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.

Registro de acceso restringido Este recurso no está disponible en acceso abierto por política de la editorial. No obstante, se puede acceder al texto completo desde la Universitat Jaume I o si el usuario cuenta con suscripción. Registre d'accés restringit Aquest recurs no està disponible en accés obert per política de l'editorial. No obstant això, es pot accedir al text complet des de la Universitat Jaume I o si l'usuari compta amb subscripció. Restricted access item This item isn't open access because of publisher's policy. The full--text version is only available from Jaume I University or if the user has a running suscription to the publisher's contents.