IBEC Seminar: Irene Marco
2019-03-01 10:00 - 12:00 (Europe/Madrid) | IBEC, floor 11, Tower I, Baldiri Reixac 4-8, 08028 Barcelona, Spain
Hyperpolarised magnetic resonance for real-time, in situ monitoring of cell metabolism
Irene Marco, Biosensors for bioengineering – IBEC
There is a clinical need for non-invasive and reliable markers to diagnose, stage and evaluate treatment response in many diseases such as cancer or non-alcoholic fatty liver disease.
Magnetic resonance (MR) methods now have the potential to revolutionise in the identification of such biomarkers in real time. Spectroscopic identification and quantitation of metabolites via carbon-13 chemical shifts can be combined with imaging (MRI) to simultaneously probe spatial (biodistribution) and temporal (kinetics) aspects of metabolism in vivo. These capabilities are enabled by so-called hyperpolarised (HP) MR techniques, including Dynamic Nuclear Polarisation (DNP), which can transiently boost the carbon-13 MR signals by several orders of magnitude, compared to traditional methods. DNP enables real-time measurement of enzymatic reactions in cell suspensions and in vivo. Multiple HP 13C-labelled substrates have provided insights in several metabolic pathways, including glycolysis, the pentose-phosphate pathway and the cellular redox state. I will present the potential of DNP to study metabolism in cell suspensions, tissue ex vivo and animals in vivo, as well as tap on the advances into the clinical translation of the technique. Also, I will talk about how we intend to implement HP MR to monitor metabolism in organs-in-chips in the lab of Javier Ramón (IBEC).

IBEC Seminar: Paul Wright
2019-03-15 10:00 - 12:00 | IBEC, floor 11, Tower I, Baldiri Reixac 4-8, 08028 Barcelona, Spain
Nanosafety research addressing public health concerns about metal oxide nanoparticles
Paul Wright, Head of RMIT Nanosafety Research Group – RMIT University
Paul Wright is Australia’s foremost expert in nanotoxicology and nanosafety, and founding co-ordinator of the Asia Nano Safe and NanoSafe Australia research networks. He is the toxicologist at RMIT University’s School of Health and Biomedical Sciences, at Bundoora in Melbourne, Australia. He heads RMIT’s Nanosafety Research Group and led RMIT’s large contribution to the Australian Consortium for the OECD’s recent nanosafety testing program. He is nanosafety advisor to the Australian Nanotechnology Network (ANN), and has directly advised several Australian Federal and state government authorities and committees on nanosafety issues. Paul is a Fellow of International Union of Pure and Applied Chemistry (IUPAC) and formerly an elected director of the Executive Committee of International Union of Toxicology (IUTOX).

IBEC Seminar: Silvia Muro
2019-03-22 10:00 - 12:00 | IBEC, floor 11, Tower I, Baldiri Reixac 4-8, 08028 Barcelona, Spain
Spread the word!
Nest Friday we are glad to present to all those who are part of the IBEC community the IBEC FASTER FUTURE programme, an initiative to accelerate our research in a collaborative way together with patients’ associations and hospitals. Everyone can be involved and we will comment the different ways to contribute to Faster Future.
This year, we have added a new project led by Dr. Silvia Muro, responsible for the Targeted therapeutics and nanodevices group, related to Parkinson’s disease, that affects millions of people around the world.
In this presentation, Silvia Muro will talk about Enabling Delivery of Therapeutics Across the Blood-Brain Barrier for Treatment of Neurodegenerative Diseases.
Get involved, we count on you!
Enabling Delivery of Therapeutics Across the Blood-Brain Barrier for Treatment of Neurodegenerative Diseases
Silvia Muro, IBEC Group Leader Targeted therapeutics and nanodevices / ICREA Research Professor

Accessing the brain is key to study its function and pathology, and for diagnostic and therapeutic purposes. Yet, this remains a formidable challenge due to the blood-brain barrier (BBB). To overcome this obstacle, new nanovehicles are being designed to cross this interface, without much translational success. A prime obstacle is the lack of knowledge on the biological regulation of these devices, as most efforts have been devoted to controling their chemical and physical properties. To brindge this gap of knowledge, we designed nanovehicles targeted to receptors of the main routes of transcytosis across endothelial barriers, i.e. clathrin-, caveolar, and cell adhesion molecule (CAM)-mediated pathways (identified in our lab), and compared their BBB transport in cellular and animal models. Targeting these three routes resulted in transport across the endothelial lining, whereas the CAM pathway was the most effective across a broad spectrum of carrier sizes and targeting valencies. This is reminiscent of the CAM function, which contributes to transcellular leukocyte migration, and it happened through a remodeling of the lipid composition of the endothelial plasmalemma and reorganization of the actin cytoskeleton. By understanding the biological regulation of this pathway, we were able to optimize carrier design parameters to enhance BBB crossing. This needed a fine balance between the ability of carriers to bind to BBB receptors at the apical (circulation) surface and to detach from them at the basolateral (brain) side. As a result, cargoes such as enzyme therapeutics for the treatment of neurological lysosomal disorders, were delivered in an active form in the brain after intravenous administration in mouse models. Our current efforts aim to implement this strategy for the development of new therapeutics against other neurodegenerative conditions, such as Parkinson’s disease.

IBEC Seminar: Jordi Guiu
2019-07-05 10:00 - 12:00 | IBEC, floor 11, Tower I, Baldiri Reixac 4-8, 08028 Barcelona, Spain
Tracing the origin of adult intestinal stem cells
Jordi Guiu, Biotech Research & Innovation Centre – University of Copenhagen
Jordi Guiu did his PhD in Anna Bigas laboratory (IMIM and Pompeu Fabra University-Barcelona) were he focused on the genetic circuitry that controls the establishment of hematopoietic stem cells during development. Then he joined Kim B. Jensen lab (Copenhagen University) as a postdoc, were he obtained a Marie Curie fellowship. His current research is focused on the specification of intestinal stem cells during development using fate mapping technologies, state of the art imaging, biophysical modeling and a plethora of sequencing techniques.
The adult small intestine is compartmentalized into villi and crypts containing post-mitotic differentiated and proliferative cells respectively. Intestinal stem cells (ISCs) located at the bottom of crypts express markers such as Lgr5 and fuel the constant replenishment of the intestinal epithelium. Importantly, the cellular origin of adult ISCs remains unknown. Prior to birth the immature fetal intestine is structurally simpler than the adult intestine. It is characterized by villi separated by a continuous region composed of proliferative intervillus cells; crypts have not formed and there is no evidence of a stem cell niche. Interestingly, intervillus cells located within the region between villi express the adult SAB marker Lgr5. Fate mapping studies have inferred the notion that fetal Lgr5 expressing cells are unique and specialized precursors for the adult ISCs. Using unbiased quantitative lineage-tracing approaches, biophysical modeling and intestinal transplantation experiments, we now demonstrate that in the fetal epithelium on-going tissue morphogenesis leads to a dynamic exchange of cells between the villi and intervillus regions and that all cells have got the potential to contribute to the adult stem cells. Moreover, we present exciting data outlining the mechanism for tissue development based on 3D imaging and live microscopy. Our results demonstrate that large-scale tissue remodeling and cell fate specification are intertwined processes. Moreover, these findings provide a direct link between the observed plasticity and cellular reprogramming of differentiating cells in adult tissue following damage, revealing that stem cell identity is an induced rather than a hardwired property.

IBEC Seminar: Nicolas Minc
2019-07-15 12:00 - 13:00 | IBEC, floor 11, Tower I, Baldiri Reixac 4-8, 08028 Barcelona, Spain
Division positioning in early embryos from mechanisms to function
Nicolas Minc, Insitut Jacques Monod, Paris, France
Nicolas Minc lab is located at the Institut Jacques Monod in Paris, and studies general problems of cell morphogenesis, ranging from the control of cell growth and shapes in single cells, to cell division in multicellular embryos. One hallmark of the lab is to combine quantitative imaging, biophysics methods and modelling to address fundamental questions in cell and developmental biology.

IBEC Seminar: Kara Spiller
2019-08-02 12:00 - 14:00 | IBEC, floor 11, Tower I, Baldiri Reixac 4-8, 08028 Barcelona, Spain
Immunomodulatory Biomaterials for Limb Salvage
Kara Spiller, School of Biomedical Engineering, Science, and Health Systems, Drexel University
Diabetes and peripheral arterial disease affect hundreds of millions of people worldwide. Patients with these conditions frequently develop chronic wounds on the lower limbs that lead to amputation, with a 5-year mortality rate as high as 77%. Macrophages, the primary cell of the innate immune system, are critical regulators of angiogenesis and wound healing. Their dysfunction is strongly implicated in arterial dysfunction, limb ischemia, and poorly healing chronic wounds. The goal of the Biomaterials and Regenerative Medicine Laboratory at Drexel University is to understand the mechanisms by which macrophages orchestrate successful angiogenesis and tissue regeneration and to develop novel biomaterial strategies that apply these principles to pathological situations, in order to ultimately prevent limb amputation. This talk will focus on the effects of temporal changes in macrophage phenotype on angiogenesis, the design of biomaterials and drug delivery systems to modulate macrophage phenotype for enhanced angiogenesis, and the development of macrophage phenotype-related biomarkers to assist in clinical decision making for a personalized medicine approach to wound care.
Dr. Kara Spiller is an Associate Professor in Drexel University’s School of Biomedical Engineering, Science, and Health Systems. Her research interests include the role of immune cells in tissue regeneration, the design of immunomodulatory biomaterials, and international engineering education. Her research is funded by the NIH, the NSF, and private foundations. Her awards include a Fulbright fellowship, the NSF CAREER award, and the United States nomination for the ASPIRE prize.

IBEC Seminar: Carlos Rodríguez Cabello
2019-10-01 10:00 - 11:00 | IBEC, floor 11, Tower I, Baldiri Reixac 4-8, 08028 Barcelona, Spain
Dynamic Systems Based on Elastin-Like Recombinamers
Carlos Rodríguez Cabello, Bioforge Lab, University of Valladolid CIBER-BBN
The use of recombinant technology in the production of macromolecule-based advanced biomaterials has caused a breakthrough increase in achievable degree of complexity and control on the molecular designs and compositions. Those recombinant macromolecules of polpeptide nature are called recombinamers. They are produced from a purely synthetic gene, in which the amino-acid sequence is not restricted to those found in naturally occurring proteins and it is dictated only by engineering design parameters. The high degree of complexity and control of the recombinamer compositions permit to reach unmatched levels of functionality in the materials produced by this way and on the systems based on them.
The development of functionality in such systems comes by to different ways. In one hand, these materials can display direct functionality. Such functionality is based on the presence in their composition of functional epitopes, typically inspired by functional epitopes found in natural proteins. The other source of functionality is the holistic functionality that emerges by the precise combination and interactions of direct functions in a precise and well designed macromolecular composition. This holistic function is particularly evident in system with a dynamic nature; systems that rearrange and respond to changes in their environment.
Examples of such dynamic systems will be presented. The examples will expand from complex 3D structures for regenerative medicine and tissue engineering that are able to incorporate a designed program of degradation and time evolution, to more fundamental matters such as the hierarchical spontaneous development of morphology and macroscopical shapes in natural and artificial systems.
Dr. Rodríguez-Cabello is a full professor at the Dept. of Condensed Matter Physics of the University of Valladolid (UVa) Spain. During his career he has been teaching courses related to physics of polymers and biomaterials science in both undergraduate and graduate levels. In 1997, he founded BIOFORGE in the UVa, which nowadays is an internationally recognized and word leading group in the field of recombinamers. His current research interests include the development of biofunctional, smart and customized protein polymers towards obtaining advanced biomedical devices.

IBEC Seminar: Martijn Gloerich
2019-10-04 10:00 - 11:00 | IBEC, floor 11, Tower I, Baldiri Reixac 4-8, 08028 Barcelona, Spain
Mechanical control of cell division
Martijn Gloerich, UMC Utrecth, Center for Molecular Medicine, Molecular Cancer Research
During development and adult tissue homeostasis, cellular behavior is controlled by signals that cells receive from their local environment. This is not limited to biochemical signals, as cell behavior can be instructed by mechanical forces exerted by neighbouring cells and the surrounding tissue. Cells sense this mechanical information through numerous molecules, including cell adhesion receptors, which translate mechanical cues into an appropriate cellular response. I will discuss our recent findings on force transduction through the cell-cell adhesion protein E-cadherin, and its central role in the mechanical control of cell division to regulate epithelial integrity and architecture.
Martijn Gloerich is Assistant Professor at the department of Molecular Cancer Research at the University Medical Center Utrecht, The Netherlands. Martijn obtained his PhD cum laude in 2011 from Utrecht University for his work on the regulation of small GTPases. Following his PhD, he received fellowships from the Netherlands Organization for Scientific Research (NWO) and Dutch Cancer Foundation (KWF) to perform postdoctoral research in the lab of James Nelson at Stanford University. Here, he gained experience with numerous microfabrication and bio-engineering techniques to study how communication between cells regulates cell behavior. In 2016 Martijn returned to the Netherlands to start his own research group at the University Medical Center Utrecht. His group uses an interdisciplinary approach to understand how cells sense and respond to mechanical forces to control tissue development and homeostasis, and how its disruption contributes to tumor progression.

IBEC Seminar: Christine Horejs
2019-11-05 16:00 - 17:00 | IBEC, floor 11, Tower I, Baldiri Reixac 4-8, 08028 Barcelona, Spain
Inside Nature Nanotechnology, an editor’s view
Christine Horejs, Nature Nanotechnology
Nature Nanotechnology was launched in October 2006 with the aim of publishing the most significant results in fundamental aspects, applications and implications on nanomaterials. In my presentation I will provide an overview of what the journal looks for in the field of nanomedicine and bioimaging, and I will give insight into the editorial process and some tips and tricks for submitting to our journal.
Christine Horejs received her MSci and PhD in nanobiotechnology from the University of Natural Resources and Life Sciences, Vienna, Austria, studying protein conformations and self-assembly using biophysical and theoretical approaches. She then joined the lab of Molly Stevens at Imperial College London, UK, investigating the extracellular matrix and cell–material interactions. In 2015, she moved to the Karolinska Institute, Sweden, conducting in vivo studies of anti-fibrotic biomaterials. In September 2017, she joined the Nature Reviews Materials team as an Associate Editor, and since July 2019 she is a Senior Editor at Nature Nanotechnology, where she is primarily responsible for nanomedicine and nanobiotechnology.
She has been invited to IBEC by Xavier Trepat

Clinical Colloquia
2019-11-15 10:00 - 12:00 | IBEC, floor 11, Tower I, Baldiri Reixac 4-8, 08028 Barcelona, Spain
Theoretical and practical aspects of biophysiotherapy
Josep Pous, Medical Director at Cematec-Teknon de Barcelona
In this clinical colloquia, the different treatment methods used in Biophysiotherapy such as Multifrequency Laser Therapy, Shock Waves, Modular Electromagnetic Waves, Mechanotherapy, Growth Factors, Stem Cells, will be exposed. The different mechanisms of action will be discussed at the cellular level such as mechanotransduction, mechanotranscription, depolarization of membarane or at the mitochondrial level through REDOX mechanisms, to achieve biological effects at the cellular and tissue levels. Biophysiotherapy aims to apply the possibilities of diagnosis and treatment of the laboratory (biosensors, nanobiosensors, quantum dots) to the medical practice with fewer drugs and fewer surgeries.
Dr. Josep Pous, specialist in Orthopedic Surgery, Traumatology and Rehabilitation, works at Cematec-Teknon of Barcelona (Center of Advanced and Technological Medicine) using the latest technologies in arthroscopy and prosthesis of the shoulder, hip, knee and ankle joints. Dr. Pous is a pioneer in the use of new non-invasive treatments for all musculoskeletal pathology and has incorporated new methods for its integral treatment.
He has been invited to IBEC by Pau Gorostiza

IBEC Seminar: Taher Saif
2019-11-22 10:00 - 12:00 | IBEC, floor 11, Tower I, Baldiri Reixac 4-8, 08028 Barcelona, Spain
Emergent living machines
Taher Saif , Professor, Mechanical Science and Engineering University of Illinois at Urbana-Champaign
Industrial revolution of the 19th century marked the onset of the era of machines that transformed societies. However, these machines cannot self assemble or heal themselves. On the other hand, since the discovery of genes, there is a considerable body of knowledge on engineering living cells. It is now possible to envision biohybrid machines with engineered living cells and scaffolds. These machines may self assemble and emerge from complex interactions between the cells and the scaffolds at various hierarchical levels. In this talk we will present two elementary biohybrid machines. They are both small scale swimmers. One of the swimmers is powered by primary rat cardiomyocytes. These cells are plated without any patterning on a scaffold which consists of a head and a tail. The cells self-orient to maximize scaffold deformation, and synchronize their beating. As a result, the tail deforms periodically and propels the swimmer forward. As a first step towards intelligent machines, the second swimmer consists of optogenetic neurons and muscle cells. It’s scaffold consists of a head and two tails. The muscle cells self assemble into myotubes around the tails, while the neurons are hosted by the head. The neurons spontaneously send out long cables of axons preferentially towards the muscle forming functional neuro functional junctions. They also form a neural network within themselves. Upon shining light, the neurons fire synchronously in a periodic fashion. The muscle contracts and bends the tails to propel the swimmer. This new generation of swimmer powered by neurons paves the way towards intelligent biohybrid machines. The central role of mechanics in the emergence of the biohybrid machines will be highlighted.
Dr Taher Saif received his BS and MS degrees in Civil Engineering from Bangladesh University of Engineering and Technology and Washington State University respectively in 1984 and 1986. He obtained his Ph.D degree in Theoretical and Applied Mechanics from Cornell University in 1993. He worked as a Post Doctoral Associate in Electrical Engineering and the National Nanofabrication Facility at Cornell University during 1993-97. He joined the Department of Mechanical Science and Engineering at the University of Illinois at Urbana-Champaign during 1997. He is curently the Gutgsell Professor in the department. His current research includes tumor micro environment, mechanics of neurons and cardiac cells, development of biological machines, and electro-thermo-mechanical behavior of nano scale metals and semiconductors.
He has been invited to IBEC by Samuel Sánchez

IBEC Seminar: Emilio Parisini
2019-11-26 10:00 - 12:00 | IBEC, floor 11, Tower I, Baldiri Reixac 4-8, 08028 Barcelona, Spain
Drugging the undruggable: towards the development of selective modulators of cadherin-mediated cell-cell adhesion
Emilio Parisi, Italian Institute of Technology (Milano) and Latvian Institute of Organic Synthesis (Riga)
Cadherins are transmembrane calcium-dependent cell adhesion proteins that mediate cellular adherens junction formation and tissue morphogenesis. Loss of cadherin-mediated adhesion has been implicated in many different steps of tumor progression such as invasion and migration, and is strongly related to cell–cell detachment and metastasis. Altered expression profiles of epithelial E-cadherin (CDH1) and neuronal N-cadherin (CDH2) have often been observed in cancer cells, most notably in the context of the epithelial-to-mesenchymal transition (EMT) process that occurs during cancer progression. Interestingly, while in the majority of carcinomas E-cadherin is down-regulated, in some epithelial ovarian cancer (EOC) cells are characterized by high expression levels of E-cadherin, which facilitates EOC cell proliferation. So far, structural and mutational studies have provided a rather detailed picture of the highly dynamic cadherin homo-dimerization mechanism. However, because of this intrinsic dynamic behavior, the rational design of small ligands targeting cadherin homophilic interactions has proved difficult. We determined the crystal structure of an E-cadherin extracellular fragment in complex with a peptidomimetic compound that partially inhibits cadherin homophilic adhesion. The structure, which is the first and to date the only crystal structure of a cadherin extracellular portion in complex with a small molecule inhibitor, reveals an unexpected binding mode and allows the identification of a druggable cadherin interface. Effective cell−cell adhesion modulators may represent potential anti-angiogenic drugs or pharmaceutical excipients to improve drug delivery across biological barriers.
Emilio Parisini is a Group Leader at the Center for Nano Science and Technology of the Istituto Italiano di Tecnologia (IIT) in Milano. After completing a PhD in Chemistry at the University of Bologna (Italy), he worked at the Universities of Göttingen (Germany), Cambridge (UK) and Harvard (USA). In his laboratory, he studies structure-function relationship in several chemical and biological systems, focusing primarily on the study of the interactions between proteins and their ligands, substrates or inhibitors. His current research interests include the functional and structural characterization of different members of the Cadherin family of cell adhesion proteins and of several different classes of enzymes for diagnostic (biosensors), therapeutic (structure-based drug design) and technological (protein and enzyme engineering) applications.
He has been invited to IBEC by Pau Gorostiza.

IBEC Seminar: Anotine Huet
2020-01-16 12:00 - 14:00 | Torre I Sala 3 Planta -1, Carrer Baldiri Reixac 4-8, Barcelona
Cochlear optical stimulation of the auditory pathway
Antoine Huet , Institut für Auditorische Neurowissenschaften, Universitätsmedizin Göttingen
Optical stimulation of spiral ganglion neurons (SGNs) in the ear for coding sound information provides an interesting alternative to electrical stimulation that is used in current cochlear implants for hearing restoration. As light can be conveniently confined in space, optical stimulation promises not only to increase the number of independent stimulation channels, but also potentially to restore temporal response of SGNs which are phase-locked to the periodicity of the sound. Sensitizing SGNs to light can be achieved either by optogenetic manipulation for expressing a light-sensitive protein, or by photopharmacological manipulation of receptors native to the cochlea.
Pioneering studies have established proof of principle of optical cochlear stimulation to restore hearing in rodent models of deafness (Hernandez et al, 2014; Wrobel, Dieter et al, 2018). More recent work from the last 2 years have demonstrated i) improvement of frequency selectivity in response to light-over electrical stimuli (Dieter et al, 2019), and ii) activation of the auditory pathway by faster opsins (i.e. shorter closing kinetics) which are more suitable for fast spiking SGNs (Mager, Lopez de la Morena et al, 2018, Keppeler et al, 2018). Finally, ongoing work, in collaboration with the team of Pau Gorostiza, is showing than a photopharmacological approach targeting AMPA receptors could be used to optically activate the auditory pathway with performance similar to current optogenetic tools.
Dr. Antoine Huet is a postdoctoral fellow in the Institute for Auditory Neuroscience (University Medical Center Göttingen) under the supervision of Prof. Dr. Tobias Moser. Dr Huet received his BS degree in Audiology from the Institut libre Marie-Haps (Brussel, Belgium) and MS degree in Audiology and auditory neuroscience from the University of Montpellier 1 (Montpellier, France). He obtained his PhD degree in Chemical and biological science for Health from the University of Montpellier 1 (Montpellier, France). He worked as a Postdoctoral fellow under the supervision of Pr. J-L. Puel and Jerome Bourien, PhD in the Institut des neurosciences de Montpellier (INSERM U1051, France) till May 2018. After, he joined the laboratory of Pr. Dr. Tobias Moser in the Institute for Auditory Neuroscience from the University Medical Center Göttingen (Germany). His current research interest include the development of viral transfer of suitable ChR variants into spiral ganglion neurons and of multichannel optical stimulation using cochlear implants with arrays of microscale light emitting diodes and waveguides, characterizing neuronal responses along the auditory pathway using physiological and behavioral methods. Thus, to finally compare optogenetic to acoustic and electric stimulation.
He has been invited to IBEC by Pau Gorostiza

IBEC Seminar: Andela Saric
2020-02-06 11:00 - 13:00 | Felix Serratosa, Baldiri Reixac, 10-12, Barcelona, Spain
How to build a biological nanomachine
Andela Saric , University College London
The molecular machinery of life is largely created via self-organisation of individual molecules into functional larger-scaled structures. Such processes are multi-scale in nature and constantly driven far from thermodynamic equilibrium. Our group develops minimal coarse-grained computer models to help understand how the assembly of a large number of macromolecules results in a functional nanomachine, as well as how such processes can go wrong, leading to diseases.
Here I will discuss the physical mechanisms behind two key biological nanomachines that operate via protein assembly – active elastic ESCRT-III filaments that remodel and cut cell membranes and split cells in two, and bacterial mechanosensitive protein channels that convert mechanical signals into chemical. I will discuss the model development, simulation results, and the mapping of the simulation data to in vivo experiments. Beyond their biological context, our findings can guide the design of artificial structures that are able to manipulate cell membranes and perform work at the nanoscale.
Andela is an Associate Professor in the Department of Physics and Astronomy and Laboratory for Molecular Cell Biology at University College London. She obtained her PhD from Columbia University in 2013, followed by postdoctoral research at the University of Cambridge. Andela works in the area of computational biological physics, developing minimal models to study biological assembly and cell remodelling. She is a recipient of the ERC Starting Grant, Royal Society University Research Fellowship, and HFSP Cross-disciplinary Fellowship.
She has been invited to IBEC by Josep Samitier

IBEC Seminar: Gema Esquiva
2020-02-07 10:00 - 12:00 | IBEC, floor 11, Tower I, Baldiri Reixac 4-8, 08028 Barcelona, Spain
Alteraciones en el sistema melanopsínico en la retinosis pigmentaria y durante el proceso de envejecimiento
Gema Esquiva , Universitat d’Alacant
La retinosis pigmentaria es la degeneración hereditaria de la retina más frecuente, siendo la cuarta causa de ceguera en el mundo. Además, en esta enfermedad, se producen alteraciones en los ritmos circadianos, esenciales para llevar una vida saludable, ya que estas alteraciones se relacionan con aumento en el estrés, insomnio, depresión y muchas otras patologías. La regulación de los ritmos circadianos se lleva a cabo a través de un tipo de células ganglionares de la retina, las células melanopsínicas.
En este trabajo se describen los diferentes tipos de células ganglionares melanopsínicas en la retina humana, en la retina de rata y en un modelo animal de retinosis pigmentaria. Además, evaluamos los cambios morfológicos y de densidad producidos en estas células, y estudiamos los efectos producidos en los patrones circadianos durante la progresiva degeneración retiniana que ocurre en esta enfermedad. También evaluamos el efecto neuroprotector de la administración de melatonina exógena.
El estudio morfológico de la retina en estos animales puso de manifiesto la existencia de 3 tipos de células melanopsínicas en rata de las cuales únicamente dos habían sido descritas hasta el momento. Por otro lado, observamos una disminución y degeneración de estas células, asociada a la retinosis pigmentaria y al envejecimiento.
Los resultados obtenidos mediante técnicas electrorretinográficas y mediante los registros de temperatura corporal y de actividad locomotora desvelaron que los animales modelo de retinosis pigmentaria tenían menor respuesta visual y una alteración de los ritmos circadianos. Los animales modelo de retinosis pigmentaria tratados con melatonina mostraron mayor respuesta visual y mejor regulación de los ritmos circadianos que los animales modelo sin tratar.
Estos resultados indican que en modelos de retinosis pigmentaria la degeneración de los fotorreceptores clásicos se acompaña de un proceso de remodelación de la retina interna que afecta al sistema melanopsínico. Deducimos que la alteración en los ritmos circadianos se manifiesta a partir de las alteraciones observadas en la densidad y en los procesos dendríticos de las células ganglionares melanopsínicas. En este sentido, la melatonina ejerce un efecto neuroprotector sobre los fotorreceptores en degeneración, conos, bastones y células melanopsínicas de la retina. Por otro lado, tras el estudio de las retinas humanas concluimos que el envejecimiento se asocia con una pérdida de densidad y arborización dendrítica de las células melanopsínicas lo que posiblemente explica la aparición más frecuente de trastornos del ritmo circadiano en personas de edad avanzada.
Ha sido invitada al IBEC por Pau Gorostiza
