A5017417129- Retinal Diseases and Treatments
- Retinal Development and Disorders
- Glaucoma and retinal disorders
- Retinal Imaging and Analysis
- Pancreatic function and diabetes
- Lysosomal Storage Disorders Research
- Animal Genetics and Reproduction
- Congenital heart defects research
- Iron Metabolism and Disorders
- Diabetes and associated disorders
- Renal and related cancers
- Adipose Tissue and Metabolism
- Neuroinflammation and Neurodegeneration Mechanisms
- Retinal and Optic Conditions
- Animal testing and alternatives
- Virus-based gene therapy research
- Retinopathy of Prematurity Studies
- Hemoglobinopathies and Related Disorders
- Trypanosoma species research and implications
- Metabolism, Diabetes, and Cancer
- Comparative Animal Anatomy Studies
- Helminth infection and control
- Barrier Structure and Function Studies
- Ocular Surface and Contact Lens
- Birth, Development, and Health
Universitat Autònoma de Barcelona
2016-2025
Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas
2013-2025
Instituto de Salud Carlos III
2021
University of Lisbon
2012-2020
Cell and Gene Therapy Catapult
2020
Centre for Research in Anthropology
2018-2019
University of Eastern Finland
2018
Kuopio University Hospital
2018
Hôpital Intercommunal de Créteil
2018
Université Paris-Est Créteil
2018
During the expansion of fat mass in obesity, vascularization adipose tissue is insufficient to maintain normoxia. Local hypoxia develops and may result altered adipokine expression, proinflammatory macrophage recruitment, insulin resistance. We investigated whether an increase angiogenesis could protect against obesity-induced and, consequently, Transgenic mice overexpressing vascular endothelial growth factor (VEGF) brown (BAT) white (WAT) were generated. Vessel formation, metabolism,...
Research Article9 July 2018Open Access Source DataTransparent process FGF21 gene therapy as treatment for obesity and insulin resistance Veronica Jimenez Center of Animal Biotechnology Gene Therapy (CBATEG), Universitat Autònoma de Barcelona, Bellaterra, Spain Department Biochemistry Molecular Biology, CIBER Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, Search more papers by this author Claudia Jambrina Estefania Casana Victor Sacristan Sergio Muñoz Sara Darriba Jordi...
To characterize the sequential events that are taking place in retinal neurodegeneration a murine model of spontaneous type 2 diabetes (db/db mouse).C57BLKsJ-db/db mice were used as diabetic animal model, and C57BLKsJ-db/+ served control group. assess chronological sequence abnormalities analysis was performed at different ages (8, 16 24 weeks). The retinas evaluated terms morphological functional [electroretinography (ERG)]. Histological markers (glial activation apoptosis) by...
For most lysosomal storage diseases (LSDs) affecting the CNS, there is currently no cure. The BBB, which limits bioavailability of drugs administered systemically, and short half-life enzymes, hamper development effective therapies. Mucopolysaccharidosis type IIIA (MPS IIIA) an autosomic recessive LSD caused by a deficiency in sulfamidase, sulfatase involved stepwise degradation glycosaminoglycan (GAG) heparan sulfate. Here, we demonstrate that intracerebrospinal fluid (intra-CSF)...
IGF-1 has been associated with the pathogenesis of diabetic retinopathy, although its role is not fully understood. Here we show that normoglycemic/normoinsulinemic transgenic mice overexpressing in retina developed most alterations seen human eye disease. A paracrine effect initiated vascular progressed from nonproliferative to proliferative retinopathy and retinal detachment. Eyes 2-month-old showed loss pericytes thickening basement membrane capillaries. In 6 months older, venule...
Pompe disease (PD) is caused by deficiency of the lysosomal enzyme acid α-glucosidase (GAA), leading to progressive glycogen accumulation and severe myopathy with muscle weakness. In Infantile-Onset PD (IOPD), death generally occurs <1 year age. There no cure for IOPD. Mouse models do not completely reproduce human IOPD severity. Our main objective was generate first rat model assess an innovative muscle-directed adeno-associated viral (AAV) vector-mediated gene therapy. rats were generated...
Purpose.: The retina contains two distinct populations of monocyte-derived cells: perivascular macrophages, and microglia. present study was undertaken to evaluate the presence function in mouse human retinas a subtype resident macrophages with scavenger function, different from microglia, physiological conditions during retinopathy. Methods.: Perivascular were characterized by means confocal microscopy, electron flow cytometry analyses. Two murine models blood–retinal barrier breakdown...
Neovascularization associated with diabetic retinopathy (DR) and other ocular disorders is a leading cause of visual impairment adult-onset blindness. Currently available treatments are merely palliative offer temporary solutions. Here, we tested the efficacy antiangiogenic gene transfer in an animal model that mimics chronic progression human DR. Adeno-associated viral (AAV) vectors serotype 2 coding for Pigment Epithelium Derived Factor (PEDF) were injected vitreous 1.5 month-old...
Diabetes is associated with severe secondary complications, largely caused by poor glycemic control. Treatment exogenous insulin fails to prevent these complications completely, leading significant morbidity and mortality. We previously demonstrated that it possible generate a "glucose sensor" in skeletal muscle through coexpression of glucokinase insulin, increasing glucose uptake correcting hyperglycemia diabetic mice. Here, we demonstrate long-term efficacy this approach large animal...
Mucopolysaccharidosis type II (MPSII) is an X-linked lysosomal storage disease characterized by severe neurologic and somatic caused deficiency of iduronate-2-sulfatase (IDS), enzyme that catabolizes the glycosaminoglycans heparan dermatan sulphate. Intravenous replacement therapy (ERT) currently constitutes only approved therapeutic option for MPSII. However, inability recombinant IDS to efficiently cross blood-brain barrier (BBB) limits ERT efficacy in treating neurological symptoms. Here,...
Gene therapy is an attractive tool for the treatment of monogenic disorders, in particular lysosomal storage diseases (LSD) caused by deficiencies secretable enzymes which neither full restoration normal enzymatic activity nor transduction all affected cells are necessary. However, some LSD such as Mucopolysaccharidosis Type IIIB (MPSIIIB) challenging because disease's main target organ brain and do not efficiently cross blood-brain barrier even if present at very high concentration...
Eicosanoids, such as leukotriene B4 (LTB4) and lipoxin A4 (LXA4), may play a key role during obesity. While LTB4 is involved in adipose tissue inflammation insulin resistance, LXA4 exert anti-inflammatory effects alleviate hepatic steatosis. Both lipid mediators derive from the same pathway, which arachidonate 5-lipoxygenase (ALOX5) its partner, 5-lipoxygenase–activating protein (ALOX5AP), are involved. ALOX5 ALOX5AP expression increased humans rodents with obesity resistance. We found that...
Blood-retinal barrier (BRB) breakdown is a key event in diabetic retinopathy and other ocular disorders that leads to increased retinal vascular permeability. This causes edema tissue damage resulting visual impairment. Insulin-like growth factor-I (IGF-I) involved these processes, although the relative contribution of systemic versus intraocular IGF-I remains controversial. Here, elucidate role this factor BRB breakdown, transgenic mice with either local or elevations have been examined....
Mutations in the gene for muscle phosphofructo-1-kinase (PFKM), a key regulatory enzyme of glycolysis, cause Type VII glycogen storage disease (GSDVII). Clinical manifestations span from severe infantile form, leading to death during childhood, classical which presents mainly with exercise intolerance. PFKM deficiency is considered as skeletal glycogenosis, but relative contribution altered glucose metabolism other tissues pathogenesis not fully understood. To elucidate this issue, we have...
Iron is essential in the retina because heme-containing enzyme guanylate cyclase modulates phototransduction rods and cones. Transferrin endocytosis classical pathway for obtaining iron from blood circulation retina. However, storage protein ferritin has been also recently proposed as an carrier. In this study, presence of Scara5 its binding to L-ferritin was investigated Our results showed that Scara5, specific receptor L-ferritin, expressed mouse human retinas many cell types, including...
Mucopolysaccharidosis type IIIA (MPSIIIA) is an inherited lysosomal storage disease caused by deficiency of sulfamidase, resulting in accumulation the glycosaminoglycan (GAG) heparan sulfate. It characterized severe progressive neurodegeneration, together with somatic alterations, which lead to death during adolescence. Here, we tested ability adeno-associated virus (AAV) vector-mediated genetic modification either skeletal muscle or liver revert already established phenotype 2-month-old...
Microaneurysms are present in healthy old-age human retinas. However, to date, no age-related pathogenic mechanism has been implicated their formation. Here, cellular senescence, a hallmark of aging and several diseases, analyzed the retina progeric mouse.Retinas were obtained from 17 nondiabetic donors mice deficient Bmi1. Cellular senescence was by immunohistochemistry, senescent-associated β-galactosidase activity assay, Sudan black B staining, conventional transmission electron...
Gene therapy is a promising therapeutic alternative for Lysosomal Storage Disorders (LSD), as it not necessary to correct the genetic defect in all cells of an organ achieve therapeutically significant levels enzyme body fluids, from which non-transduced can uptake protein correcting their enzymatic deficiency. Animal models are instrumental development new treatments LSD. Here we report generation first mouse model LSD Muccopolysaccharidosis Type IIID (MPSIIID), also known Sanfilippo...