Choroidal Vessel Wall: Hypercholesterolaemia-Induced Dysfunction and Potential Role of Statins

© 2012 Ramírez et al., licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Unidad Docente de Inmunología, Oftalmología y ORLFac. de Óptica y OptometríaTRUEMinisterio de Ciencia e Innovación de EspañaFundación Mutua MadrileñaUniversidad Complutense de Madridpu

The Role of Autophagy in Eye Diseases

This research was funded by the Ophthalmological Network OFTARED (Enfermedades oculares: Prevención, detección precoz, tratamiento y rehabilitación de las patologías oculares) (RD16/0008/0005 and RD16/0008/0026) of the Institute of Health of Carlos III of the Spanish Ministry of Economy and by the European programme FEDER; and Network RETiBRAIN (La retina un modelo para investigar Neuroprotección en patologías del Sistema Nervioso Central) (RED2018-102499-T) of Spanish Ministry of Science and Innovation. And J.A.F.-A. is currently funded by a Predoctoral Fellowship (FPU17/01023) from the Spanish Ministry of Science, Innovation, and Universities; and I.L.-C. is currently funded by a Predoctoral Fellowship (CT42/18-CT43/18) from the Complutense University of Madrid.Autophagy is a catabolic process that ensures homeostasis in the cells of our organism. It plays a crucial role in protecting eye cells against oxidative damage and external stress factors. Ocular pathologies of high incidence, such as age-related macular degeneration, cataracts, glaucoma, and diabetic retinopathy are of multifactorial origin and are associated with genetic, environmental factors, age, and oxidative stress, among others; the latter factor is one of the most influential in ocular diseases, directly affecting the processes of autophagy activity. Alteration of the normal functioning of autophagy processes can interrupt organelle turnover, leading to the accumulation of cellular debris and causing physiological dysfunction of the eye. The aim of this study is to review research on the role of autophagy processes in the main ocular pathologies, which have a high incidence and result in high costs for the health system. Considering the role of autophagy processes in cell homeostasis and cell viability, the control and modulation of autophagy processes in ocular pathologies could constitute a new therapeutic approach.Depto. de Inmunología, Oftalmología y ORLFac. de MedicinaTRUEUnión EuropeaMinisterio de Ciencia e Innovación (España)Instituto de Salud Carlos IIIUniversidad Complutense de Madridpu

Retinal Macroglial Responses in Health and Disease

Due to their permanent and close proximity to neurons, glial cells perform essential tasks for the normal physiology of the retina. Astrocytes andM¨uller cells (retinal macroglia) provide physical support to neurons and supplement them with several metabolites and growth factors.Macroglia are involved in maintaining the homeostasis of extracellular ions and neurotransmitters, are essential for information processing in neural circuits, participate in retinal glucose metabolism and in removing metabolic waste products, regulate local blood flow, induce the blood-retinal barrier (BRB), play fundamental roles in local immune response, and protect neurons from oxidative damage. In response to polyetiological insults, glia cells react with a process called reactive gliosis, seeking to maintain retinal homeostasis. When malfunctioning, macroglial cells can become primary pathogenic elements. A reactive gliosis has been described in different retinal pathologies, including age-related macular degeneration (AMD), diabetes, glaucoma, retinal detachment, or retinitis pigmentosa. A better understanding of the dual, neuroprotective, or cytotoxic effect of macroglial involvement in retinal pathologies would help in treating the physiopathology of these diseases.The extensive participation of the macroglia in retinal diseases points to these cells as innovative targets for new drug therapies

Effects of Hypercholesterolaemia in the Retina

© 2012 Triviño et al., licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Unidad Docente de Inmunología, Oftalmología y ORLFac. de Óptica y OptometríaTRUEMinisterio de Ciencia e Innovación (MICINN)Fundación Mutua MadrileñaUniversidad Complutense de Madridpu

Modelo de planeación de producción para una empresa del sector de cereales

En este trabajo de grado se realizó la planeación de la producción de una empresa del sector de cereales. Se planteó un modelo matemático que integra la planeación maestra de la producción, el plan de requerimientos de materia prima y el plan de requerimientos de distribución, a su vez se ajusta a los requerimientos de la empresa. Posteriormente, se transcribió el modelo a un archivo Python para darle solución con el optimizador CPLEX. Se creó una interfaz en Excel en donde se puede ejecutar el modelo y visualizar los resultados más relevantes a través un dashboard. Finalmente, se midió el impacto a través de los indicadores de rendimiento logístico OTIF e Infull, comparando los datos históricos y los obtenidos por el modelo.In this project, a production plan was designed for a company in the cereal sector. A mathematical model was adjusted to the company ́s needs integrating Master Production Scheduling, Material Requirement Planning and Distribution Requirement Planning. Subsequently, the model was transcribed into a Python file in order to solve said model through CPLEX optimizer. Then, a user interface was created in Excel, where this model can be executed and the most relevant results can be visualize using a dashboard. Finally, the impact was measured with the contrast of the historical logistics performance indicators (OTIF and Infull) and the ones obtained with the model.Ingeniero (a) IndustrialPregrad

“Super p53” Mice Display Retinal Astroglial Changes

Tumour-suppressor genes, such as the p53 gene, produce proteins that inhibit cell division under adverse conditions, as in the case of DNA damage, radiation, hypoxia, or oxidative stress (OS). The p53 gene can arrest proliferation and trigger death by apoptosis subsequent to several factors. In astrocytes, p53 promotes cell-cycle arrest and is involved in oxidative stress-mediated astrocyte cell death. Increasingly, astrocytic p53 is proving fundamental in orchestrating neurodegenerative disease pathogenesis. In terms of ocular disease, p53 may play a role in hypoxia due to ischaemia and may be involved in the retinal response to oxidative stress (OS). We studied the influence of the p53 gene in the structural and quantitative characteristics of astrocytes in the retina. Adult mice of the C57BL/6 strain (12 months old) were distributed into two groups: 1) mice with two extra copies of p53 (“super p53”; n = 6) and 2) wild-type p53 age-matched control, as the control group (WT; n = 6). Retinas from each group were immunohistochemically processed to locate the glial fibrillary acidic protein (GFAP). GFAP+ astrocytes were manually counted and the mean area occupied for one astrocyte was quantified. Retinal-astrocyte distribution followed established patterns; however, morphological changes were seen through the retinas in relation to p53 availability. The mean GFAP+ area occupied by one astrocyte in “super p53” eyes was significantly higher (p<0.05; Student’s t-test) than in the WT. In addition, astroglial density was significantly higher in the “super p53” retinas than in the WT ones, both in the whole-retina (p<0,01 Student’s t-test) and in the intermediate and peripheral concentric areas of the retina (p<0.05 Student’s t-test). This fact might improve the resistance of the retinal cells against OS and its downstream signalling pathways

Ocular Exploration in the Diagnosis and Follow-Up of the Alzheimer’s Dementia

The retina is part of the central nervous system (CNS), and therefore, in Alzheimer’s disease (AD), retinal and optic nerve degeneration could take place. This degeneration leads to neurofunctional changes that can be detected early and followed up throughout the evolution of the disease. As opposed to other CNS structures, the eye is easily accessible for in vivo observation. Retinal organization allows for the identification of its different neurons, and in consequence, detection of minimal changes taking place during neurodegeneration is possible. Functional vision studies performed on AD patients in recent years have shown how visual acuity, contrast sensitivity, color vision, and visual integration vary with the progression of neurodegeneration. The development of optical coherence tomography in ophthalmology has meant a breakthrough in retinal exploratory techniques, allowing the obtention of high-resolution images using light. This technique enables retinal analysis in the earliest stages of AD, being considered as a biomarker of neuronal damage. Given AD’s high prevalence and its expected increase, it is important to perform easy tests that cause minimal discomfort to the patients at a low cost while offering abundant information on the stage of the disease

Automatic Counting of Microglial Cells in Healthy and Glaucomatous Mouse Retinas

Proliferation of microglial cells has been considered a sign of glial activation and a hallmark of ongoing neurodegenerative diseases. Microglia activation is analyzed in animal models of different eye diseases. Numerous retinal samples are required for each of these studies to obtain relevant data of statistical significance. Because manual quantification of microglial cells is time consuming, the aim of this study was develop an algorithm for automatic identification of retinal microglia. Two groups of adult male Swiss mice were used: age-matched controls (naïve, n = 6) and mice subjected to unilateral laser-induced ocular hypertension (lasered; n = 9). In the latter group, both hypertensive eyes and contralateral untreated retinas were analyzed. Retinal whole mounts were immunostained with anti Iba-1 for detecting microglial cell populations. A new algorithm was developed in MATLAB for microglial quantification; it enabled the quantification of microglial cells in the inner and outer plexiform layers and evaluates the area of the retina occupied by Iba-1+ microglia in the nerve fiber-ganglion cell layer. The automatic method was applied to a set of 6,000 images. To validate the algorithm, mouse retinas were evaluated both manually and computationally; the program correctly assessed the number of cells (Pearson correlation R = 0.94 and R = 0.98 for the inner and outer plexiform layers respectively). Statistically significant differences in glial cell number were found between naïve, lasered eyes and contralateral eyes (P<0.05, naïve versus contralateral eyes; P<0.001, naïve versus lasered eyes and contralateral versus lasered eyes). The algorithm developed is a reliable and fast tool that can evaluate the number of microglial cells in naïve mouse retinas and in retinas exhibiting proliferation. The implementation of this new automatic method can enable faster quantification of microglial cells in retinal pathologies

Macular Thickness as a Potential Biomarker of Mild Alzheimer's Disease

Although several postmortem findings in the retina of patients with Alzheimer's disease (AD) are available, new biomarkers for early diagnosis and follow-up of AD are still lacking. It has been postulated that the defects in the retinal nerve fiber layer (RNFL) may be the earliest sign of AD, even before damage to the hippocampal region that affects memory. This fact may reflect retinal neuronal-ganglion cell death and axonal loss in the optic nerve in addition to aging

High-resolution copy number analysis of paired normal-tumor samples from diffuse large B cell lymphoma

Copy number analysis can be useful for assessing prognosis in diffuse large B cell lymphoma (DLBCL). We analyzed copy number data from tumor samples of 60 patients diagnosed with DLBCL de novo and their matched normal samples. We detected 63 recurrent copy number alterations (CNAs), including 33 gains, 30 losses, and nine recurrent acquired copy number neutral loss of heterozygosity (CNN-LOH). Interestingly, 20 % of cases acquired CNN-LOH of 6p21 locus, which involves the HLA region. In normal cells, there were no CNAs but we observed CNN-LOH involving some key lymphoma regions such as 6p21 and 9p24.1 (5 %) and 17p13.1 (2.5 %) in DLBCL patients. Furthermore, a model with some specific CNA was able to predict the subtype of DLBCL, 1p36.32 and 10q23.31 losses being restricted to germinal center B cell-like (GCB) DLBCL. In contrast, 8p23.3 losses and 11q24.3 gains were strongly associated with the non-GCB subtype. A poor prognosis was associated with biallelic inactivation of TP53 or 18p11.32 losses, while prognosis was better in cases carrying 11q24.3 gains. In summary, CNA abnormalities identify specific DLBCL groups, and we describe CNN-LOH in germline cells from DLBCL patients that are associated with genes that probably play a key role in DLBCL development.This work was supported by research funding from the Health Council of Castilla y León (GRS265/A/08), the Health Research Program (PS09/01382), and the Red Temática de Investigación Cooperativa en Cáncer (RTICC) grant RD12/0036 (groups 0069, 0029, 0036, 0058, and 0060) included in the National Plan I+D+I supported by the Instituto Carlos III and the Fondo Europeo de Desarrollo Regional (FEDER), the Spanish Ministry of Economy and Competitiveness, and the European Regional Development Fund (ERDF) 'Una manera de hacer Europa' (Innocampus; CEI-2010-1-0010). ES was supported by CM10/00078-Río Hortega, an ISCIII contract, FEHH grant 2013–2014 and JR14/00025-Juan Rodés, an ISCIII contract. IS was supported by the Subprograma Juan de la Cierva (JCI-2011-10232) and a Miguel Servet contract (CP13/00159).Peer Reviewe