Martin Heidegger y Ludwig Wittgenstein: Los límites de la filosofía.

Sin resume

Martin Heidegger y Ludwig Wittgenstein: Los límites de la filosofía.

Sin resume

Astrocytes and Müller Cell Alterations During Retinal Degeneration in a Transgenic Rat Model of Retinitis Pigmentosa

Purpose: Retinitis pigmentosa includes a group of progressive retinal degenerative diseases that affect the structure and function of photoreceptors. Secondarily to the loss of photoreceptors, there is a reduction in retinal vascularization, which seems to influence the cellular degenerative process. Retinal macroglial cells, astrocytes, and Müller cells provide support for retinal neurons and are fundamental for maintaining normal retinal function. The aim of this study was to investigate the evolution of macroglial changes during retinal degeneration in P23H rats. Methods: Homozygous P23H line-3 rats aged from P18 to 18 months were used to study the evolution of the disease, and SD rats were used as controls. Immunolabeling with antibodies against GFAP, vimentin, and transducin were used to visualize macroglial cells and cone photoreceptors. Results: In P23H rats, increased GFAP labeling in Müller cells was observed as an early indicator of retinal gliosis. At 4 and 12 months of age, the apical processes of Müller cells in P23H rats clustered in firework-like structures, which were associated with ring-like shaped areas of cone degeneration in the outer nuclear layer. These structures were not observed at 16 months of age. The number of astrocytes was higher in P23H rats than in the SD matched controls at 4 and 12 months of age, supporting the idea of astrocyte proliferation. As the disease progressed, astrocytes exhibited a deteriorated morphology and marked hypertrophy. The increase in the complexity of the astrocytic processes correlated with greater connexin 43 expression and higher density of connexin 43 immunoreactive puncta within the ganglion cell layer (GCL) of P23H vs. SD rat retinas. Conclusions: In the P23H rat model of retinitis pigmentosa, the loss of photoreceptors triggers major changes in the number and morphology of glial cells affecting the inner retina

Epitaxial growth of biferroic YMnO3(0001) on platinum electrodes

Epitaxial films of the biferroic YMnO3 (YMO) oxide have been grown on platinum-coated SrTiO3(1 1 1) and Al2O3(0 0 0 1) substrates. The platinum electrodes, (1 1 1) oriented, are templates for the epitaxy of the hexagonal phase of YMO with a (0 0 0 1) out-of-plane orientation, which is of interest as this is the polarization direction of YMO. X-ray diffractometry indicates the presence of two crystal domains, 60° rotated in-plane, in the Pt(1 1 1) layers which subsequently are transferred on the upperlaying YMO. Cross-section analysis by high-resolution transmission electron microscopy (HRTEM) of YMnO3/Pt/SrTiO3(1 1 1) shows high-quality epitaxy and sharp interfaces across the structure in the observed region. We present a detailed study of the epitaxial growth of the hexagonal YMO on the electrodes

Kerr measurements on single-domain SrRuO3 thin films

We report on the magneto-optical measurements of an epitaxial SrRuO3 film grown on SrTiO3 (0 0 1), which previously was determined to be single domain orientated by x-ray diffraction and Raman spectroscopy techniques. Our experiments reveal a large Kerr rotation, which reaches a maximum value of about 0.5° at low temperature. By measuring magnetic hysteresis loops at different temperatures, we determined the temperature dependence of the Kerr rotation in the polar configuration. Values of the anisotropic magnetoresistance ~ 20% have been measured. These values are remarkably higher than those of other metallic oxides such as manganites. This striking difference can be attributed to the strong spin-orbit interaction of the Ru 4d ion in the SrRuO3 compound

Retinal Thickness Changes Over Time in a Murine AD Model APP NL-F/NL-F.

Background: Alzheimer's disease (AD) may present retinal changes before brain pathology, suggesting the retina as an accessible biomarker of AD. The present work is a diachronic study using spectral domain optical coherence tomography (SD-OCT) to determine the total retinal thickness and retinal nerve fiber layer (RNFL) thickness in an APPNL-F/NL-F mouse model of AD at 6, 9, 12, 15, 17, and 20 months old compared to wild type (WT) animals. Methods: Total retinal thickness and RNFL thickness were determined. The mean total retinal thickness was analyzed following the Early Treatment Diabetic Retinopathy Study sectors. RNFL was measured in six sectors of axonal ring scans around the optic nerve. Results: In the APPNL-F/NL-F group compared to WT animals, the total retinal thickness changes observed were the following: (i) At 6-months-old, a significant thinning in the outer temporal sector was observed; (ii) at 15-months-old a significant thinning in the inner temporal and in the inner and outer inferior retinal sectors was noticed; (iii) at 17-months-old, a significant thickening in the inferior and nasal sectors was found in both inner and outer rings; and (iv) at 20-months-old, a significant thinning in the inner ring of nasal, temporal, and inferior retina and in the outer ring of superior and temporal retina was seen. In RNFL thickness, there was significant thinning in the global analysis and in nasal and inner-temporal sectors at 6 months old. Thinning was also found in the supero-temporal and nasal sectors and global value at 20 months old. Conclusions: In the APPNL-F/NL-F AD model, the retinal thickness showed thinning, possibly produced by neurodegeneration alternating with thickening caused by deposits and neuroinflammation in some areas of the retina. These changes over time are similar to those observed in the human retina and could be a biomarker for AD. The APPNL-F/NL-F AD model may help us better understand the different retinal changes during the progression of AD.This research was funded by the Ophthalmological Network OFTARED (RD16/0008/0005) of the Institute of Health of Carlos III of the Spanish Ministry of Science and Innovation; and the Research Network RETIBRAIN (RED2018-102499-T) and Grant PID2019-106581RB-I00 of the Spanish Ministry of Science and Innovation; and Leducq Foundation for Cardiovascular Research TNE-19CVD01. IL-C was currently supported by a Pre-doctoral Fellowship (CT42/18-CT43/18) from the Complutense University of Madrid. JF-A was currently supported by a Pre-doctoral Fellowship (FPU17/01023) from the Spanish Ministry of Science, Innovation, and Universities.S

Microglial Hemoxygenase-1 Deletion Reduces Inflammation in the Retina of Old Mice with Tauopathy

Tauopathies 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.Depto. de Inmunología, Oftalmología y ORLUnidad Docente de Inmunología, Oftalmología y ORLFac. de MedicinaFac. de Óptica y OptometríaTRUEMinisterio de Ciencia e Innovación de EspañaMinisterio de Ciencia, Innovación y Universidades de EspañaUniversidad Complutense de Madridpu

Characterization of retinal drusen in subjects at high genetic risk of developing sporadic Alzheimer’s disease: An exploratory analysis

Having a family history (FH+) of Alzheimer’s disease (AD) and being a carrier of at least one ε4 allele of the ApoE gene are two of the main risk factors for the development of AD. AD and age-related macular degeneration (AMD) share one of the main risk factors, such as age, and characteristics including the presence of deposits (Aβ plaques in AD and drusen in AMD); however, the role of apolipoprotein E isoforms in both pathologies is controversial. We analyzed and characterized retinal drusen by optical coherence tomography (OCT) in subjects, classifying them by their AD FH (FH-or FH+) and their allelic characterization of ApoE ε4 (ApoE ε4-or ApoE ε4+) and considering cardiovascular risk factors (hypercholesterolemia, hypertension, and diabetes mellitus). In addition, we analyzed the choroidal thickness by OCT and the area of the foveal avascular zone with OCTA. We did not find a relationship between a family history of AD or any of the ApoE isoforms and the presence or absence of drusen. Subjects with drusen show choroidal thinning compared to patients without drusen, and thinning could trigger changes in choroidal perfusion that may give rise to the deposits that generate drusen

Glaucoma: from pathogenic mechanisms to retinal glial cell response to damage

Glaucoma is a neurodegenerative disease of the retina characterized by the irreversible loss of retinal ganglion cells (RGCs) leading to visual loss. Degeneration of RGCs and loss of their axons, as well as damage and remodeling of the lamina cribrosa are the main events in the pathogenesis of glaucoma. Different molecular pathways are involved in RGC death, which are triggered and exacerbated as a consequence of a number of risk factors such as elevated intraocular pressure (IOP), age, ocular biomechanics, or low ocular perfusion pressure. Increased IOP is one of the most important risk factors associated with this pathology and the only one for which treatment is currently available, nevertheless, on many cases the progression of the disease continues, despite IOP control. Thus, the IOP elevation is not the only trigger of glaucomatous damage, showing the evidence that other factors can induce RGCs death in this pathology, would be involved in the advance of glaucomatous neurodegeneration. The underlying mechanisms driving the neurodegenerative process in glaucoma include ischemia/hypoxia, mitochondrial dysfunction, oxidative stress and neuroinflammation. In glaucoma, like as other neurodegenerative disorders, the immune system is involved and immunoregulation is conducted mainly by glial cells, microglia, astrocytes, and Müller cells. The increase in IOP produces the activation of glial cells in the retinal tissue. Chronic activation of glial cells in glaucoma may provoke a proinflammatory state at the retinal level inducing blood retinal barrier disruption and RGCs death. The modulation of the immune response in glaucoma as well as the activation of glial cells constitute an interesting new approach in the treatment of glaucoma