Caractérisation de la rétinopathie induite par la lumière chez le rat nouveau-né

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal

Stability of Perfectly Matched Layers, Group Velocities and Anisotropic Waves

Perfectly Matched Layers (PML) are a recent technique for simulating the absorption of waves in open domains. They have been introduced for electromagn- etic waves and extended, since then, to other models of wave propagation, including waves in elastic anisotropic media. In this last case, some numerical experiments have shown that the PMLs are not always stable. In this paper, we investigate this question from a theoretical point of view. In the first part, we derive a necessary condition for the stability of the PML model for a general hyperbolic system. This condition can be interpreted in terms of geometrical properties of the slowness diagrams and used for explaining instabilities observed with elastic waves but also with other propagation models (anisotropic Maxwell's equations, linearize- d Euler equations). In the second part, we specialize our analysis to orthotropic elastic waves and obtain separately a necessary stability condition and a sufficient stability condition that can be expressed in terms of inequalities on the elasticity coefficients of the model

B cell-dependent EAE induces visual deficits in the mouse with similarities to human autoimmune demyelinating diseases.

BACKGROUND In the field of autoimmune demyelinating diseases, visual impairments have extensively been studied using the experimental autoimmune encephalomyelitis (EAE) mouse model, which is classically induced by immunization with myelin oligodendrocyte glycoprotein peptide (MOG35-55). However, this model does not involve B cells like its human analogs. New antigens have thus been developed to induce a B cell-dependent form of EAE that better mimics human diseases. METHODS The present study aimed to characterize the visual symptoms of EAE induced with such an antigen called bMOG. After the induction of EAE with bMOG in C57BL/6J mice, visual function changes were studied by electroretinography and optomotor acuity tests. Motor deficits were assessed in parallel with a standard clinical scoring method. Histological examinations and Western blot analyses allowed to follow retinal neuron survival, gliosis, microglia activation, opsin photopigment expression in photoreceptors and optic nerve demyelination. Disease effects on retinal gene expression were established by RNA sequencing. RESULTS We observed that bMOG EAE mice exhibited persistent loss of visual acuity, despite partial recovery of electroretinogram and motor functions. This loss was likely due to retinal inflammation, gliosis and synaptic impairments, as evidenced by histological and transcriptomic data. Further analysis suggests that the M-cone photoreceptor pathway was also affected. CONCLUSION Therefore, by documenting visual changes induced by bMOG and showing similarities to those seen in diseases such as multiple sclerosis and neuromyelitis optica, this study offers a new approach to test protective or restorative ophthalmic treatments

Predicting glucocorticoid resistance in multiple sclerosis relapse via a whole blood transcriptomic analysis.

AIMS Treatment of multiple sclerosis (MS) relapses consists of short-term administration of high-dose glucocorticoids (GCs). However, over 40% of patients show an insufficient response to GC treatment. We aimed to develop a predictive model for such GC resistance. METHODS We performed a receiver operating characteristic (ROC) curve analysis following the transcriptomic assay of whole blood samples from stable, relapsing GC-sensitive and relapsing GC-resistant patients with MS in two different European centers. RESULTS We identified 12 genes being regulated during a relapse and differentially expressed between GC-sensitive and GC-resistant patients with MS. Using these genes, we defined a statistical model to predict GC resistance with an area under the curve (AUC) of the ROC analysis of 0.913. Furthermore, we observed that relapsing GC-resistant patients with MS have decreased GR, DUSP1, and TSC22D3 mRNA levels compared with relapsing GC-sensitive patients with MS. Finally, we showed that the transcriptome of relapsing GC-resistant patients with MS resembles those of stable patients with MS. CONCLUSION Predicting GC resistance would allow patients to benefit from prompt initiation of an alternative relapse treatment leading to increased treatment efficacy. Thus, we think our model could contribute to reducing disability development in people with MS

Invasiveness of an introduced species: the role of hybridization and ecological constraints

International audienceIntroduced species are confronted with new environments to which they need to adapt. However, the ecological success of an introduced species is generally difficult to predict, especially when hybridizations may be involved in the invasion success. In western Europe, the lake frog Pelophylax ridibundus appears to be particularly successful. A reason for this species' success might be the presence of the invader's genetic material prior to the introduction in the form of a hybrid between P. ridibundus and a second indigenous water frog species. These hybrids reproduce by hybridogenesis, only transmitting the ridibundus genome to gametes and backcrossing with the indigenous species (i.e. P. lessonae). This reproductive system allows the hybrid to be independent from P. ridibundus, and allows the ridibundus genome to be more widely spread than the species itself. Matings among hybrids produce newly formed P. ridibundus offspring (N), if the genomes are compatible. Therefore, we hypothesize that hybridogenesis increases the invasiveness of P. ridibundus (1) by enhancing propagule pressure through N individuals, and/or (2) by increasing adaptation of invaders to the native water frogs' habitat through hybrid-derived ridibundus genomes that are locally adapted. We find support for the first hypothesis because a notable fraction of N tadpoles is viable. However, in our semi-natural experiments they did not outperform ridibundus tadpoles in the native water frogs' habitat, nor did they differ physiologically. This does not support the second hypothesis and highlights ecological constraints on the invasion. However, we cannot rule out that these constraints may fall with ongoing selection, making a replacement of indigenous species highly probable in the future

Human Tau Expression Does Not Induce Mouse Retina Neurodegeneration, Suggesting Differential Toxicity of Tau in Brain vs. Retinal Neurons

The implication of the microtubule-associated protein (MAP) Tau in the ocular manifestations of Alzheimer’s disease (AD) is elusive due to the lack of relevant animal model. However, signs of AD have been reported in the brain of transgenic mice expressing human Tau (hTau). To assess whether hTau is sufficient to induce AD pathogenesis in the retina as well, in the present study, we compared the retinal structure and function of KO mice deprived of Tau (mTKO) with those of transgenic mice expressing hTau. Our results revealed that hTau is particularly abundant in the inner nuclear layer (INL) cells of the retina. By electroretinogram (ERG) recording, light-induced retinal cell activation was not altered in hTau compared with mTKO littermates. Surprisingly, the ERG response mediated by cone photoreceptor stimulation was even stronger in hTau than in mTKO retinae. Immunofluorescent analysis of retinal sections allowed us to observe thicker inner retina in hTau than in mTKO eyes. By Western Blotting (WB), the upregulation of mTOR that was found in hTau mice may underlie retinal structure and function increases. Taken together, our results not only indicate that hTau expression is not toxic for retinal cells but they also suggest that it may play a positive role in visual physiology. The use of hTau may be envisaged to improve visual recovery in ocular diseases affecting the retinal function such as glaucoma or diabetic retinopathy

Preferential Transfer of Certain Plasma Membrane Proteins onto T and B Cells by Trogocytosis

T and B cells capture antigens via membrane fragments of antigen presenting cells (APC) in a process termed trogocytosis. Whether (and how) a preferential transfer of some APC components occurs during trogocytosis is still largely unknown. We analyzed the transfer onto murine T and B cells of a large panel of fluorescent proteins with different intra-cellular localizations in the APC or various types of anchors in the plasma membrane (PM). Only the latter were transferred by trogocytosis, albeit with different efficiencies. Unexpectedly, proteins anchored to the PM's cytoplasmic face, or recruited to it via interaction with phosphinositides, were more efficiently transferred than those facing the outside of the cell. For proteins spanning the PM's whole width, transfer efficiency was found to vary quite substantially, with tetraspanins, CD4 and FcRγ found among the most efficiently transferred proteins. We exploited our findings to set immunodiagnostic assays based on the capture of preferentially transferred components onto T or B cells. The preferential transfer documented here should prove useful in deciphering the cellular structures involved in trogocytosis