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MSCA Expressions of Interest 2017

Jesus Pintor
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Bioquímica y Biología Molecular IV
Faculty of Optics and Optometry
Scientific and technical history of the last five years of the research group “Pharmacological Biochemistry of the Eye (OCUPHARM)”.
OcuPharm research group belongs to the School of Optometry at the Complutense University of Madrid. It is exploiting its scientific expertise in the fields of biochemistry, pharmacology, ocular pathology, molecular biology, molecular pathology and neurology. The group has a number of commercial collaborations in place, providing services to biotechnology companies in basic science and preclinical studies regarding medicines, biochemical, pharmacological and physiology to the eye and its diseases. From the year 2007 up to the year 2010, the research group participated in one FP-6 EU project (ARTEMIS) as coordinator and in another FP-6 project (UPDATE) as partner. The project UPDATE that was finished in 2010 was dedicated to the student training and had the title “Understanding and Providing a Developmental Approach to Technology Education”.In the year 2015 the group was granted an H2020 EU project for the development of a biomarker for Dry Eye syndrome.Since its creation from the Prof. Jesus Pintor in 1998, the research group is focusing its scientific activities on the research of melatonin effects and its analogy on the intraocular pressure (IOP), corneal wound healing, Dry Eye syndrome, Glaucoma, and Ocular surface pathologies.The director of the group is the Full Professor, Jesus Pintor, PhD and he will be the scientific supervisor for the student Nery Garcia Porta.The group and especially its director has extensive experience in the training of pre and post-doctoral students.From the year 2007 to 2010 we participated in a national network of 9 participants, for student exchange in the sector of research related to eye neurotransmission called NEUROTRANS.The group is constantly participating in scientific student exchange and the last years we received several PhD students for stays from national universities and international universities from Greece, Israel and USA. We have sent as well a student for a 4 year postdoc stay in New York University School of Medicine in the USA, establishing mutual beneficial relations with this university. Since 2008 and at least up to the year 2017 the group is participating in a scientific network for the connection of 20 Ophthalmological, mainly clinical, research groups in Spain, called RETICS. The network is dedicated among others to the scientific exchange of students and researchers, among the participant groups.The group was responsible for the successful presentation of 10 doctoral thesis for the last 5 years and currently is directing another 11 doctoral thesis projects.
Among the members of the group are:
Director Dr Jesus Pintor PhD in Biochemistry
Dr. Gonzalo Carracedo PhD in Optometry
Dr. Almudena Crooke PhD in Biochemistry
Dr. Ana Isabel Guzman PhD in Chemistry
Dr. Alba Martin PhD in Optometry
Dr. Patricia Loma PhD in Optometry
Dr. Maria Jesus Perez PhD in Biochemistry
Dr. Fernando Huete PhD in Biochemistry
WEB: www.ocupharm.com
ADDRESS: C / Arcos De Jalon 118 28037 Madrid
Tel. 913946859
Fax. 913946885
Technologies used
Cell cultures (primary cultures and cell lines), Optical and confocal microscopy, Immunocytochemistry and immunohistochemistry, Western-blot, PCR and RT-PCR, Microfluorimetry, Spectrophotometry, HPLC, Ocular imaging techniques, Histological studies, Animal models of glaucoma
Basic research
Ocular Pharmacology, Location receptor, Immunohistochemistry, Immunocytochemistry, ocular Biochemistry, studies messengers and receptors, Immune-localization of enzymes, enzyme kinetics, molecular biology, Cloning of receptors and enzymes, gene silencing siRNA testing and verification, Cell Culture, primary cell cultures and cell lines, corneal epithelial cells, trabecular meshwork, ciliary epithelial cells.
Pre-clinical research
Ocular hypertension and glaucoma drugs tests New Zealand White rabbits-normotensive and hypertensive, corneal scarring, "In vivo" studies of corneal healing, "In vitro" studies of corneal healing, lacrimation, dry eye, tear secretion studies, Diagnosis in dry eye, corneal neovascularization, angiogenesis inhibitors Tests, Contact Lenses, technology support contact lenses.
Clinical Research
In collaboration with the clinic of the Faculty of Optics
Group productivity
Scientific publications: 202 (179 + 23 books magazines and book chapters)
Patents: 24
Projects and research contracts: 65
Intraocular pressure-Melatonin and intraocular pressure
During 2000 and until now our group has worked intensively to understand the role of melatonin and its analogues on intraocular pressure. At that time the company INSPIRE PHARMACEUTICALS contacted us because of our interest in research on the effects of nucleotides on intraocular pressure. After the knowledge of our experiments with melatonin and analogues, that company has designed new analogues of melatonin which have been tested in our laboratory. The interest of this company in the search for more effective melatonin analogues reducing the intraocular pressure, leaving in the background the cellular and molecular mechanisms, the subject of this project.The gains we've made on the issue have been, first, to describe that topical application of melatonin and the compound 5-MCA-NAT reduces intraocular pressure very significantly. This effect was found that is mediated by a receptor for melatonin because it could be inhibited with the non-selective antagonist luzindole. Another of the most important aspects of this work was presented prolonged effect in particular compound 5-MCA-NAT (5 carboxyamido methyl N-acetyl tryptamine). This suggested that this compound, with the hypotensive property so marked and prolonged effect that could be employed in the treatment of ocular hypertension.In a second publication we characterize the receptor responsible for such hypotensive action based on the pharmacology with melatonin agonists, 2-phenyl-melatonin melatonin 6-chloro-2-iodo-melatonin, 5-MCA-NAT and N-acetyl tryptamine in addition to the antagonist’s prazosin, 4-P-DH-PDOT and 97. This article allowed to verify that the melatonin receptor closely resembles the MT3 defined as that to date only been described by ligand binding studies. Also in this study it was found the link between the melatonin receptor and nervous system that controls the production and drainage of aqueous humor.Today our interest is to continue this line of work a deeper understanding of how melatonin mode and its receptors are connected to the nervous system that controls such an important physiologically as intraocular pressure process.
Nucleotides and intraocular pressure
Since 1998 we are working on the study of the nucleotide and its physiological role in the eye. We started with the effect of mononucleotides, ATP and the like, on intraocular pressure finding some compounds with hypotensive properties of interesting, such as methylene ATP and ATP-methylene intraocular pressure. Then we turn to study the effect of polyphosphates diadenosine on intraocular pressure (IOP), finding that the Ap4A also had a hypotensive effect type. In addition to the work described in the attached references, these jobs have been transferred to the OTRI (transfer office and research results) and obtained two patents, one national and one European on the subject.In this same line of work, but at a more superficial eye level, we studied the presence of polyphosphates in tears diadenosine rabbit and human. In the model of New Zealand rabbits we have succeeded in demonstrating the presence of polyphosphates diadenosine Ap3A, Ap4A and AP5A at micromolar concentrations. We have also been shown that topical application of these compounds promotes tear secretion in a dose dependent. We have observed that the receptors that mediate tear secretion are P2Y2 receptor type would be found and located on the main lacrimal gland. In humans, we have described the presence of polyphosphates diadenosine AP5A Ap4A and, although we have not done experiments to measure tear secretion induced by these dinucleotides.
Lacrimation, corneal scarring and nucleotides
This part of the investigation arises from a macroscopic level work in New Zealand rabbits. All this idea came the discovery of the presence of polyphosphates diadenosine as natural constituent of tears, both human and animal models. Nucleotides and dinucleotides are not only present in the tear rabbit and human tear but also when they are instilled drop form are able to increase the tear secretion, which in this case, especially useful for the treatment of dry eye . Have found these substances in the tear, he made us think about the possibility that these molecules and other nucleotides have a role as reepithelization agents for corneal injury. So, we launched a model of corneal injury in rabbits New Zealand based on superficial lesions produce discs Whatman paper soaked in n-heptanol. The great advantage of this method is fidelity when repeated and therefore can perform quantitative measures. Thus, we found that the lesions produced with n-heptanol were healing faster when nucleotides are added as the UTP and Ap4A (10 nmol). Comparatively, resurfacing accelerated between 25 and 60%, so that lesions disappeared long before when corneas were left to heal on their own. The variation in the rate of healing was shown to be dependent on nucleotide / dinucleotide tested and its concentration. Also, we try to study what kind of purinergic receptor was responsible for such action (P2X or P2Y), for which besides numerous test agonists antagonists were also tested. Thus, it was possible to verify that the nucleotide reepitelizador effect was reversed by P2Y receptor antagonists such as suramin or blue reagent 2 (RB-2). In a step further, and taking into account the limitations of the fact of working with a live animal, study the possible second messengers that mediate the action of these nucleotides. Therefore, inhibitors of protein kinase C (PKC), such as staurosporine, which significantly reduced reepitelizante effect of nucleotides were employed. Delving a little deeper into the cascade of intracellular events that happen after stimulation of P2Y receptor, we note that the use of inhibitors of MAP kinase cascade, U-0126 or the AG-1478 and tyrosine kinase inhibitors produced a remarkable decrease effect of healing cup nucleotides.
Life Sciences (LIF)
2017-07-15 00:00:00
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