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
Identifiers
4 results
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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 Retinal Molecular Changes Are Associated with Neuroinflammation and Loss of RGCs in an Experimental Model of Glaucoma(International Journal of Molecular Sciences, 2021) Fernández Arrabal, José A.; Salazar Corral, Juan José; Hoz Montañana, María Rosa de; Marco López, Eva María; Martín Sánchez, Beatriz; Flores Salguero, Elena; García Martín, Elena Salobrar; López Cuenca, Inés; Barrios Sabador, Vicente; Avilés Trigueros, Marcelino; Valiente Soriano, Francisco Javier; Miralles de Imperial-Ollero, Juan A.; Vidal Sanz, Manuel; Triviño Casado, Alberto; Ramirez Sebastian, Jose Manuel; López Gallardo, Meritxell; Ramírez Sebastián, Ana IsabelSignaling mediated by cytokines and chemokines is involved in glaucoma-associated neuroinflammation and in the damage of retinal ganglion cells (RGCs). Using multiplexed immunoassay and immunohistochemical techniques in a glaucoma mouse model at different time points after ocular hypertension (OHT), we analyzed (i) the expression of pro-inflammatory cytokines, anti-inflammatory cytokines, BDNF, VEGF, and fractalkine; and (ii) the number of Brn3a+ RGCs. In OHT eyes, there was an upregulation of (i) IFN-γ at days 3, 5, and 15; (ii) IL-4 at days 1, 3, 5, and 7 and IL-10 at days 3 and 5 (coinciding with downregulation of IL1-β at days 1, 5, and 7); (iii) IL-6 at days 1, 3, and 5; (iv) fractalkine and VEGF at day 1; and (v) BDNF at days 1, 3, 7, and 15. In contralateral eyes, there were (i) an upregulation of IL-1β at days 1 and 3 and a downregulation at day 7, coinciding with the downregulation of IL4 at days 3 and 5 and the upregulation at day 7; (ii) an upregulation of IL-6 at days 1, 5, and 7 and a downregulation at 15 days; (iii) an upregulation of IL-10 at days 3 and 7; and (iv) an upregulation of IL-17 at day 15. In OHT eyes, there was a reduction in the Brn3a+ RGCs number at days 3, 5, 7, and 15. OHT changes cytokine levels in both OHT and contralateral eyes at different time points after OHT induction, confirming the immune system involvement in glaucomatous neurodegeneration.Item Retinal Changes in Astrocytes and Müller Glia in a Mouse Model of Laser-Induced Glaucoma: A Time-Course Study(Biomedicines, 2022) Fernández Albarral, José Antonio; Hoz Montañana, María Rosa de; Matamoros, José A.; Chen, Leijing; López Cuenca, Inés; García Martín, Elena Salobrar; Sánchez Puebla, Lídia; Ramirez Sebastian, Jose Manuel; Triviño Casado, Alberto; Salazar Corral, Juan José; Ramírez Sebastián, Ana IsabelMacroglia (astrocytes and Müller glia) may play an important role in the pathogenesis of glaucoma. In a glaucoma mouse model, we studied the effects of unilateral laser-induced ocular hypertension (OHT) on macroglia in OHT and contralateral eyes at different time points after laser treatment (1, 3, 5, 8 and 15 days) using anti-GFAP and anti-MHC-II, analyzing the morphological changes, GFAP-labelled retinal area (GFAP-PA), and GFAP and MHC-II immunoreactivity intensities ((GFAP-IRI and MHC-II-IRI)). In OHT and contralateral eyes, with respect to naïve eyes, at all the time points, we found the following: (i) astrocytes with thicker somas and more secondary processes, mainly in the intermediate (IR) and peripheral retina (PR); (ii) astrocytes with low GFAP-IRI and only primary processes near the optic disc (OD); (iii) an increase in total GFAP-RA, which was higher at 3 and 5 days, except for at 15 days; (iv) an increase in GFAP-IRI in the IR and especially in the PR; (v) a decrease in GFAP-IRI near the OD, especially at 1 and 5 days; (vi) a significant increase in MHC-II-IRI, which was higher in the IR and PR; and (vii) the Müller glia were GFAP+ and MHC-II+. In conclusion, in this model of glaucoma, there is a bilateral macroglial activation maintained over time involved in the inflammatory glaucoma process.