Oxidative Stress as a Main Contributor of Retinal Degenerative Diseases

This research was funded by DGA group B08_17R: Investigación en Retina y Sistema Visual and Fondo Europeo de Desarrollo Regional (FEDER) funds: “Una manera de hacer Europa”, Ministerio de Ciencia e Innovación (FEDER-PID 2019-106230RB-I00), Instituto de Salud Carlos III (PI20/00740-FEDER, RETICS-FEDER RD16/0008/0016), and Generalitat Valenciana (PROMETEO/2021/024)

Role of IFN-gamma in immune responses to Candida albicans infections

Candida albicans is the most frequent etiologic agent that causes opportunistic fungal infections called candidiasis, a disease whose systemic manifestation could prove fatal and whose incidence is increasing as a result of an expanding immunocompromised population. Here we review the role of interferon-gamma (IFN-γ) in host protection against invasive candidiasis. This cytokine plays an essential role in both the innate and adaptive arms of the immune response to candidiasis. We focus on recent progress on host-pathogen interactions leading to the production of IFN-γ by host cells. IFN-γ is produced by CD4 Th1, CD8, γδ T, and natural killer (NK) cells, essentially in response to both IL-12 and/or IL-18; more recently, a subset of C. albicans-specific Th17 cells have been described to produce both IL-17 and IFN-γ. IFN-γ plays an important role in the regulation of the immune system as well as in the control of the infectious process, as it is required for optimal activation of phagocytes, collaborates in the generation of protective antibody response, and favors the development of a Th1 protective response.Research in the M.L. Gil and D. Gozalbo laboratory is supported by Grant SAF2010-18256 (Ministerio de Economia y Competitividad, Spain)

Cultivo de células ganglionares de retina bovina

Comunicación presentada a la XXVII Reunión del GEN (Grupo Español de Neurotransmisión), Chiclana (Cádiz), 12-16 diciembre 2006Este trabajo ha sido financiado por la Universidad de Alicante (Ayudas a Grupos Jóvenes, GRJ05-14) y por la Generalitat Valenciana (GV05/151)

Experiencia docente de farmacología en un grupo de estudiantes adultos

La contribución de la Universidad al conocimiento y desarrollo es fundamental para el avance y el bienestar de la sociedad. Además de encargarse de la formación en la educación superior y de contribuir al desarrollo científico y tecnológico, la Universidad difunde el conocimiento a la sociedad mediante la extensión universitaria y la formación continua. Presentamos en este trabajo una experiencia que realizamos con un grupo de estudiantes de más de 50 años, inscritos en un curso de iniciación a la Farmacología. Exponemos la utilización de diversas técnicas docentes que incluyen la clase magistral, prácticas en laboratorio, talleres de búsqueda de información sobre medicamentos en Internet, resolución de casos clínicos y el planteamiento de actividades transversales, como la elaboración de vídeos para un concurso internacional. Con algunas diferencias entre ellas, las actividades fueron en general muy bien acogidas y valoradas por los estudiantes. La experiencia resultó muy positiva también para los docentes, que encontramos estudiantes motivados, participativos y casi podríamos decir que entusiastas.The contribution of the University to the knowledge and the development of the society is essential for its progress and welfare. In addition to the educational objective and contributing to scientific and technological development, the University disseminates knowledge to society through programs of continuous training. In this work we present an experience carried out with a group of students over 50 years old, enrolled in an introductory course in Pharmacology. We present the use of different teaching techniques that include master classes, laboratory practices, workshops to learn how to search for pharmacology-related information on the Internet, the resolution of clinical cases and also a transversal activity, the creation of Pharmacology-related videos for an international contest. With some differences between them, the activities were generally very well evaluated by the students. The experience was also very positive for the teachers, as we found highly motivated students, with a high participation and almost enthusiastic

Combined drug triads for synergic neuroprotection in retinal degeneration

This review focuses on retina degeneration occurring during glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), and retinitis pigmentosa (RP), and on the potential therapeutic use of triads of repositioned medicines, addressed to distinct but complementary targets, to prevent, delay or stop retina cell death. Although myriad pathogenic mechanisms have been implicated in these disorders, common signaling pathways leading to apoptotic cell death to all of them, and to all neurodegenerative diseases are (i) calcium dyshomeostasis/excitotoxicity; (ii) oxidative stress/mitochondrial dysfunction, and (iii) neuroinflammation/P2X7 receptor activation. From a therapeutic point of view, it is relevant to consider the multitarget approach based on the use of combined medicines acting on complementary pathogenic mechanisms that has been highly successful in the treatment of chronic diseases such as cancer, AIDS, pain, hypertension, Parkinson’s disease, cardiac failure, depression, or the epilepsies as the basic mechanisms of cell death do not differ between the different CNS degenerative diseases. We suggest the multi-target therapy approach could be more effective compared with single-drug treatments. Used at doses lower than standard, these triads may also be safer and more efficient. After the establishment of a proof-of-concept in animal models of retinal degeneration, potential successful preclinical trials of such combinations may eventually drive to test this concept in clinical trials in patients, first to evaluate the safety and efficacy of the drug combinations in humans and then their therapeutic advantages, if any, seeking the prevention and/or the delay of retina degeneration and blindness.We thank the support received from the EU Horizon 2020 Research and Innovation Program under Maria Slodowska‐Curie, Grant/Award Number: Grant Agreement N. 766124; Fundación Teófilo Hernando; Spanish Ministry of Science and Innovation (FEDER-PID2019-106230RB-I00) and Generalitat Valenciana (IDIFEDER/2017/064, PROMETEO/2021/024)

Persistent inflammatory state after photoreceptor loss in an animal model of retinal degeneration

Microglia act as the resident immune cells of the central nervous system, including the retina. In response to damaging stimuli microglia adopt an activated state, which can progress into a phagocytic phenotype and play a potentially harmful role by eliciting the expression and release of pro-inflammatory cytokines. The aim of the present study was to assess longitudinal changes in microglia during retinal degeneration in the homozygous P23H rat, a model of dominant retinitis pigmentosa. Microglial phenotypes, morphology and density were analyzed by immunohistochemistry, flow cytometry, and cytokine antibody array. In addition, we performed electroretinograms to evaluate the retinal response. In the P23H retina, sclera, choroid and ciliary body, inflammatory cells increased in number compared with the control at all ages analyzed. As the rats became older, a higher number of amoeboid MHC-II+ cells were observed in the P23H retina, which correlated with an increase in the expression of pro-inflammatory cytokines. These findings suggest that, in the P23H model, retinal neuroinflammation persists throughout the rat’s life span even after photoreceptor depletion. Therefore, the inclusion of anti-inflammatory drugs at advanced stages of the neurodegenerative process may provide better retinal fitness so the remaining cells could still be used as targets of cellular or gene therapies.This work was supported by grants from the Spanish Ministry of the Economy and Competitiveness-FEDER (BFU2012-36845, BFU2015-67139-R), Instituto de Salud Carlos III (RETICS-FEDER RD12/0034/0010), Organización Nacional de Ciegos Españoles (ONCE), Asociación Retina Asturias, FUNDALUCE and Fundación Jesús de Gangoiti Barrera

Natural Compounds from Saffron and Bear Bile Prevent Vision Loss and Retinal Degeneration

All retinal disorders, regardless of their aetiology, involve the activation of oxidative stress and apoptosis pathways. The administration of neuroprotective factors is crucial in all phases of the pathology, even when vision has been completely lost. The retina is one of the most susceptible tissues to reactive oxygen species damage. On the other hand, proper development and functioning of the retina requires a precise balance between the processes of proliferation, differentiation and programmed cell death. The life-or-death decision seems to be the result of a complex balance between pro- and anti-apoptotic signals. It has been recently shown the efficacy of natural products to slow retinal degenerative process through different pathways. In this review, we assess the neuroprotective effect of two compounds used in the ancient pharmacopoeia. On one hand, it has been demonstrated that administration of the saffron constituent safranal to P23H rats, an animal model of retinitis pigmentosa, preserves photoreceptor morphology and number, the capillary network and the visual response. On the other hand, it has been shown that systemic administration of tauroursodeoxycholic acid (TUDCA), the major component of bear bile, to P23H rats preserves cone and rod structure and function, together with their contact with postsynaptic neurons. The neuroprotective effects of safranal and TUDCA make these compounds potentially useful for therapeutic applications in retinal degenerative diseases.This research was supported by grants from the Spanish Ministry of Economy and Competitiveness-FEDER (BFU2012-36845), Instituto de Salud Carlos III (RETICS RD12/0034/0010), Asociación Retina Asturias, Fundación Jesús Gangoiti, Organización Nacional de Ciegos Españoles (ONCE) and FUNDALUCE

In vitro differentiation of murine hematopoietic progenitor cells toward the myeloid lineage occurs in response to Staphylococcus aureus and yeast species

We have studied the effect of inactivated microbial stimuli (Candida albicans, Candida glabrata, Saccharomyces boulardii, and Staphylococcus aureus) on the in vitro differentiation of lineage negative (Lin−) hematopoietic progenitor mouse cells. Purified Lin− progenitors were co-cultured for 7 days with the stimuli, and cell differentiation was determined by flow cytometry analysis. All the stimuli assayed caused differentiation toward the myeloid lineage. S. boulardii and particularly C. glabrata were the stimuli that induced in a minor extent differentiation of Lin− cells, as the major population of differentiated cells corresponded to monocytes, whereas C. albicans and S. aureus induced differentiation beyond monocytes: to monocyte-derived dendritic cells and macrophages, respectively. Interestingly, signaling through TLR2 by its pure ligand Pam3CSK4 directed differentiation of Lin− cells almost exclusively to macrophages. These data support the notion that hematopoiesis can be modulated in response to microbial stimuli in a pathogen-dependent manner, being determined by the pathogen-associated molecular patterns and the pattern-recognition receptors involved, in order to generate the populations of mature cells required to deal with the pathogen.Research was supported by grants: SAF2010-18256 (Ministerio de Economía y Competitividad, Spain) and ACOMP/2013/168 (Generalitat Valenciana, Valencia, Spain)

Experiencia de clase inversa

El uso de herramientas multimedia ofrece una serie de oportunidades de mejora del proceso de enseñanza-aprendizaje. El recurso de clase inversa se ha mostrado como una herramienta útil en el proceso de aprendizaje, que permite mejorar los resultados alcanzados en una clase tradicional. Permite además una interacción más personalizada entre el docente y el estudiante y estimula el trabajo autónomo de los alumnos. Experiencia previa de parte del grupo en este tipo de enseñanza, si bien en otra materia, mostraba cómo esta metodología permite profundizar más en los contenidos a desarrollar, puesto que los alumnos llegan a clase con un bagaje previo. Así decidimos realizar una experiencia piloto de clase inversa en un seminario de farmacología. Antes de asistir al seminario, los estudiantes debían visualizar un vídeo que elaboramos previamente y rellenar un cuestionario de autoevaluación para detectar posibles lagunas. Durante el seminario se resolvieron las dudas sobre la materia y se realizó el cuestionario de evaluación. Los alumnos manifestaron que el vídeo les había resultado útil para la comprensión de la materia y se mostraron satisfechos con la actividad. Consideramos que esta metodología es exportable a los temas de teoría y abre una nueva vía de inclusión de contenidos