Person: López Cuenca, Inés
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First Name
Inés
Last Name
López Cuenca
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Medicina
Department
Inmunología, Oftalmología y ORL
Area
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7 results
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Item Foveal Avascular Zone and Choroidal Thickness Are Decreased in Subjects with Hard Drusen and without High Genetic Risk of Developing Alzheimer’s Disease(Biomedicines, 2021) López Cuenca, Inés; Hoz Montañana, María Rosa de; Alcántara Rey, Celia; García Martín, Elena Salobrar; Elvira Hurtado, Lorena; Fernández Albarral, José Antonio; Barabash, Ana; Ramírez Toraño, Federico; Frutos Lucas, Jaisalmer de; Salazar Corral, Juan José; Ramírez Sebastián, Ana Isabel; Ramirez Sebastian, Jose ManuelA family history (FH+) of Alzheimer’s disease (AD) and ε4 allele of the ApoE gene are the main genetic risk factors for developing AD, whereas ε4 allele plays a protective role in age-related macular degeneration. Ocular vascular changes have been reported in both pathologies. We analyzed the choroidal thickness using optical coherence tomography (OCT) and the foveal avascular zone (FAZ) using OCT-angiography and compared the results with ApoE gene expression, AD FH+, and the presence or absence of hard drusen (HD) in 184 cognitively healthy subjects. Choroidal thickness was statistically significantly different in the (FH−, ε4−, HD+) group compared with (i) both the (FH−, ε4−, HD−) and the (FH+, ε4+, HD+) groups in the superior and inferior points at 1500 µm, and (ii) the (FH+, ε4−, HD+) group in the superior point at 1500 µm. There were statistically significant differences in the superficial FAZ between the (FH+, ε4−, HD+) group and (i) the (FH+, ε4−, HD−) group and (ii) the (FH+, ε4+, HD−) group. In conclusion, ocular vascular changes are not yet evident in participants with a genetic risk of developing AD.Item Microglial Activation in the Retina of a Triple-Transgenic Alzheimer’s Disease Mouse Model (3xTg-AD)(International Journal of Molecular Sciences, 2020) García Martín, Elena Salobrar; Rodríguez Neves, Ana C.; Ramírez Sebastián, Ana Isabel; Hoz Montañana, María Rosa de; Fernández Albarral, José Antonio; López Cuenca, Inés; Ramirez Sebastian, Jose Manuel; Ambrósio, Antonio Francisco; Salazar Corral, Juan JoséAlzheimer’s disease (AD) is the most common type of dementia in the world. The main biomarkers associated with AD are protein amyloid-β (Aβ) plaques and protein tau neurofibrillary tangles, which are responsible for brain neuroinflammation mediated by microglial cells. Increasing evidence has shown that the retina can also be affected in AD, presenting some molecular and cellular changes in the brain, such as microglia activation. However, there are only a few studies assessing such changes in the retinal microglia in animal models of AD. These studies use retinal sections, which have some limitations. In this study, we performed, for the first time in a triple-transgenic AD mouse model (3xTg-AD), a quantitative morphometric analysis of microglia activation (using the anti-Iba-1 antibody) in retinal whole-mounts, allowing visualization of the entire microglial cell, as well as its localization along the extension of the retina in different layers. Compared to age-matched animals, the retina of 3xTg-AD mice presents a higher number of microglial cells and a thicker microglial cell body area. Moreover, the microglia migrate, reorient, and retract their processes, changing their localization from a parallel to a perpendicular position relative to the retinal surface. These findings demonstrate clear microglia remodeling in the retina of 3xTg-AD mice.Item Microglial Hemoxygenase-1 Deletion Reduces Inflammation in the Retina of Old Mice with Tauopathy(Antioxidants, 2022) Fernández Albarral, José Antonio; García Martín, Elena Salobrar; Matamoros, José A.; Fernández Mendivil, Cristina; Sastre, Eric, del; Chen, Leijing; Hoz Montañana, María Rosa de; López Cuenca, Inés; Sánchez Puebla, Lídia; Ramirez Sebastian, Jose Manuel; Salazar Corral, Juan José; García López, Manuela (Manuela G. López); Ramírez Sebastián, Ana IsabelTauopathies such as Alzheimer’s disease are characterized by the accumulation of neurotoxic aggregates of tau protein. With aging and, especially, in Alzheimer’s patients, the inducible enzyme heme oxygenase 1 (HO-1) progressively increases in microglia, causing iron accumulation, neuroinflammation, and neurodegeneration. The retina is an organ that can be readily accessed and can reflect changes that occur in the brain. In this context, we evaluated how the lack of microglial HO-1, using mice that do not express HO-1 in microglia (HMO-KO), impacts retinal macro and microgliosis of aged subjects (18 months old mice) subjected to tauopathy by intrahippocampal delivery of AAV-hTauP301L (TAU). Our results show that although tauopathy, measured as anti-TAUY9 and anti-AT8 positive immunostaining, was not observed in the retina of WT-TAU or HMO-KO+TAU mice, a morphometric study of retinal microglia and macroglia showed significant retinal changes in the TAU group compared to the WT group, such as: (i) increased number of activated microglia, (ii) retraction of microglial processes, (iii) increased number of CD68+ microglia, and (iv) increased retinal area occupied by GFAP (AROA) and C3 (AROC3). This retinal inflammatory profile was reduced in HMO-KO+TAU mice. Conclusion: Reduction of microglial HO-1 could be beneficial to prevent tauopathy-induced neuroinflammation.Item Retinal Tissue Shows Glial Changes in a Dravet Syndrome Knock-in Mouse Model(International Journal of Molecular Sciences, 2023) Salazar Corral, Juan José; Satriano, Andrea; Matamoros, José A.; Fernández Albarral, José; García Martín, Elena Salobrar; López Cuenca, Inés; Hoz Montañana, María Rosa De; Sánchez-Puebla Fernández, Lidia; Ramírez Sebastián, José Manuel; Alonso, Cristina; Satta, Valentina; Hernández Fisac, Inés; Sagredo Ezquioga, Onintza; Ramírez Sebastián, Ana IsabelDravet syndrome (DS) is an epileptic encephalopathy caused by mutations in the Scn1a gene encoding the α1 subunit of the Nav1.1 sodium channel, which is associated with recurrent and generalized seizures, even leading to death. In experimental models of DS, histological alterations have been found in the brain; however, the retina is a projection of the brain and there are no studies that analyze the possible histological changes that may occur in the disease. This study analyzes the retinal histological changes in glial cells (microglia and astrocytes), retinal ganglion cells (RGCs) and GABAergic amacrine cells in an experimental model of DS (Syn-Cre/Scn1aWT/A1783V) compared to a control group at postnatal day (PND) 25. Retinal whole-mounts were labeled with anti-GFAP, anti-Iba-1, anti-Brn3a and anti-GAD65/67. Signs of microglial and astroglial activation, and the number of Brn3a+ and GAD65+67+ cells were quantified. We found retinal activation of astroglial and microglial cells but not death of RGCs and GABAergic amacrine cells. These changes are similar to those found at the level of the hippocampus in the same experimental model in PND25, indicating a relationship between brain and retinal changes in DS. This suggests that the retina could serve as a possible biomarker in DS.Item The Role of Citicoline and Coenzyme Q10 in Retinal Pathology(International Journal of Molecular Sciences, 2023) García López, Claudia; García López, Verónica; Matamoros Felipe, José Antonio; Fernández Albarral, José; García Martín, Elena Salobrar; Hoz Montañana, María Rosa De; López Cuenca, Inés; Sánchez-Puebla Fernández, Lidia; Ramírez Sebastian, Jose Manuel; Ramírez Sebastián, Ana Isabel; Salazar Corral, Juan JoséOcular neurodegenerative diseases such as glaucoma, diabetic retinopathy, and age-related macular degeneration are common retinal diseases responsible for most of the blindness causes in the working-age and elderly populations in developed countries. Many of the current treatments used in these pathologies fail to stop or slow the progression of the disease. Therefore, other types of treatments with neuroprotective characteristics may be necessary to allow a more satisfactory management of the disease. Citicoline and coenzyme Q10 are molecules that have neuroprotective, antioxidant, and anti-inflammatory properties, and their use could have a beneficial effect in ocular neurodegenerative pathologies. This review provides a compilation, mainly from the last 10 years, of the main studies that have been published on the use of these drugs in these neurodegenerative diseases of the retina, analyzing the usefulness of these drugs in these pathologies.Item Is saffron able to prevent the dysregulation of retinal cytokines induced by ocular hypertension in mice?(Journal of Clinical Medicine, 2021) Fernández Albarral, José Antonio; Martínez López, Miguel Ángel; Marco López, Eva María; Hoz Montañana, María Rosa De; Martín Sánchez, Beatriz; San Felipe Riba, Diego; García Martín, Elena Salobrar; López Cuenca, Inés; Pinazo Durán, Mª Dolores; Salazar Corral, Juan José; Ramírez Sebastián, José Manuel; López-Gallardo, Meritxell; Ramírez Sebastián, Ana IsabelCytokine- and chemokine-mediated signalling is involved in the neuroinflammatory process that leads to retinal ganglion cell (RGC) damage in glaucoma. Substances with anti-inflammatory properties could decrease these cytokines and chemokines and thus prevent RGC death. The authors of this study analysed the anti-inflammatory effect of a hydrophilic saffron extract standardized to 3% crocin content, focusing on the regulation of cytokine and chemokine production, in a mouse model of unilateral laser-induced ocular hypertension (OHT). We demonstrated that following saffron treatment, most of the concentration of proinflammatory cytokines (IL-1β, IFN-γ, TNF-α, and IL-17), anti-inflammatory cytokines (IL-4 and IL-10), Brain-derived Neurotrophic Factor (BDNF), Vascular Endothelial Growth Factor (VEGF), and fractalkine were unaffected in response to laser-induced OHT in both the OHT eye and its contralateral eye. Only IL-6 levels were significantly increased in the OHT eye one day after laser induction compared with the control group. These results differed from those observed in animals subjected to unilateral OHT and not treated with saffron, where changes in cytokine levels occurred in both eyes. Therefore, saffron extract regulates the production of proinflammatory cytokines, VEGF, and fractalkine induced by increasing intraocular pressure (IOP), protecting the retina from inflammation. These results indicate that saffron could be beneficial in glaucoma by helping to reduce the inflammatory processItem Microglial changes in the early aging stage in a healthy retina and an experimental glaucoma model(Glaucoma: A Neurodegenerative Disease of the Retina and Beyond - Part A, 2020) Ramírez Sebastián, Ana Isabel; Fernández Albarral, José Antonio; Hoz Montañana, Rosa de; López Cuenca, Inés; García Martín, Elena Salobrar; Rojas Lozano, Pilar; Valiente Soriano, Francisco Javier; Avilés Trigueros, Marcelino; Villegas Pérez, María Paz; Vidal Sanz, Manuel; Triviño Casado, Alberto; Salazar Corral, Juan José; Ramirez Sebastian, Jose Manuel; Bagetta, Giacinto; Nucci, CarloGlaucoma is an age-related neurodegenerative disease that begins at the onset of aging. In this disease, there is an involvement of the immune system and therefore of the microglia. The purpose of this study is to evaluate the microglial activation using a mouse model of ocular hypertension (OHT) at the onset of aging. For this purpose, we used both naive and ocular hypertensives of 15-month-old mice (early stage of aging). In the latter, we analyzed the OHT eyes and the eyes contralateral to them to compare them with their aged controls. In the eyes of aged naive, aged OHT and aged contralateral eyes, microglial changes were observed compared to the young mice, including: (i) aged naive vs young naive: An increased soma size and vertical processes; (ii) aged OHT eyes vs young OHT eyes: A decrease in the area of the retina occupied by Iba-1 cells and in vertical processes; and (iii) aged contralateral vs young contralateral: A decrease in the soma size and arbor area and an increase in the number of microglia in the outer segment layer. Aged OHT eyes and the eyes contralateral to them showed an up-regulation of the CD68 expression in the branched microglia and a down-regulation in the MHCII and P2RY12 expression with respect to the eyes of young OHT mice. Conclusion: in the early phase of aging, morphological microglial changes along with changes in the expression of MHCII, CD68 and P2RY12, in both naive and OHT mice. These changes appear in aged OHT eyes and the eyes contralateral to them eyes.