45 research outputs found
Effects of rat anti-VEGF antibody in a rat model of corneal graft rejection by topical and subconjunctival routes
PURPOSE: To compare the effect of a rat anti-VEGF antibody, administered either by topical or subconjunctival (SC) routes, on a rat model of corneal transplant rejection.METHODS: Twenty-four rats underwent corneal transplantation and were randomized into four treatment groups (n=6 in each group). G1 and G2 received six SC injections (0.02 ml 10 ”g/ml) of denatured (G1) or active (G2) anti-VEGF from Day 0 to Day 21 every third day. G3 and G4 were instilled three times a day with denatured (G3) or active (G4) anti-VEGF drops (10 ”g/ml) from Day 0 to Day 21. Corneal mean clinical scores (MCSs) of edema (E), transparency (T), and neovessels (nv) were recorded at Days 3, 9, 15, and 21. Quantification of neovessels was performed after lectin staining of vessels on flat mounted corneas.RESULTS: Twenty-one days after surgery, MCSs differed significantly between G1 and G2, but not between G3 and G4, and the rejection rate was significantly reduced in rats receiving active antibodies regardless of the route of administration (G2=50%, G4=66.65% versus G1 and G3=100%; p<0.05). The mean surfaces of neovessels were significantly reduced in groups treated with active anti-VEGF (G2, G4). However, anti-VEGF therapy did not completely suppress corneal neovessels.CONCLUSIONS: Specific rat anti-VEGF antibodies significantly reduced neovascularization and subsequent corneal graft rejection. The SC administration of the anti-VEGF antibody was more effective than topical instillation
Novel drug delivery systems targeting intraocular tissues
The availability of new therapeutic molecules for the management of chronic intraocular diseases
has highlighted the deficiency of drug delivery systems for their administration. New research programs
on drug delivery methods designed to reduce the administration frequency have led to the
development of various polymers, biodegradable or not, that release therapeutic molecules directly
into the vitreous cavity. Two innovating ocular delivery methods are now available, based on the use
of electrical current: iontophoresis, a non-invasive intraocular delivery method for various molecules,
and plasmid electroporation into the ciliary muscle, in which the muscle produces a therapeutic molecule
directly inside the posterior chamber for several months. In the near future, we will be able to
administer therapeutic molecules to treat a specific disease using a method of administration targeting
a specific intraocular tissue.La mise sur le marché de
molécules innovantes pour le traitement des maladies oculaires chroniques a révélé la
pauvreté des moyens de les administrer, mais elle a aussi ouvert la voie à la recherche dans
ce domaine. Dans le but de limiter la fréquence des administrations, des polymÚres,
biodégradables ou non, ont été développés pour libérer des principes actifs directement dans
la cavité vitréenne. L'utilisation du courant électrique est à l'origine de deux techniques
d'administration innovantes: l'iontophorĂšse, qui permet d'administrer des principes actifs
en intraoculaire sans aucune effraction, et l'Ă©lectroporation de plasmide dans le muscle
ciliaire, qui permet de faire produire par ce muscle une molécule thérapeutique, directement
dans la chambre postérieure, et ce pendant plusieurs mois. Dans le futur proche, pour chaque
maladie nécessitant un principe actif particulier, nous disposerons d'une méthode adaptée
d'administration ciblant spécifiquement un tissu oculaire
Neurotrophins are expressed in giant cell arteritis lesions and may contribute to vascular remodeling
International audienceIntroduction: Giant cell arteritis (GCA) is characterized by intimal hyperplasia leading to ischaemic manifestations that involve large vessels. Neurotrophins (NTs) and their receptors (NTRs) are protein factors for growth, differentiation and survival of neurons. They are also involved in the migration of vascular smooth muscle cells (VSMCs). Our aim was to investigate whether NTs and NTRs are involved in vascular remodelling of GCA.Methods: We included consecutive patients who underwent a temporal artery biopsy for suspected GCA. We developed an enzymatic digestion method to obtain VSMCs from smooth muscle cells in GCA patients and controls. Neurotrophin protein and gene expression and functional assays were studied from these VSMCs. Neurotrophin expression was also analysed by immunohistochemistry in GCA patients and controls.Results: Whereas temporal arteries of both GCA patients (nâ=â22) and controls (nâ=â21) expressed nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB) and sortilin, immunostaining was more intense in GCA patients, especially in the media and intima, while neurotrophin-3 (NT-3) and P75 receptor (P75NTR) were only detected in TA from GCA patients. Expression of TrkB, a BDNF receptor, was higher in GCA patients with ischaemic complications. Serum NGF was significantly higher in GCA patients (nâ=â28) vs. controls (nâ=â48), whereas no significant difference was found for BDNF and NT-3. NGF and BDNF enhanced GCA-derived temporal artery VSMC proliferation and BDNF facilitated migration of temporal artery VSMCs in patients with GCA compared to controls.Conclusions: Our results suggest that NTs and NTRs are involved in vascular remodelling of GCA. In GCA-derived temporal artery VSMC, NGF promoted proliferation and BDNF enhanced migration by binding to TrkB and p75NTR receptors. Further experiments are needed on a larger number of VSMC samples to confirm these results
Increased Phosphorylation of Vimentin in Noninfiltrative Meningiomas
International audienceBACKGROUND: Tissue invasion or tissue infiltration are clinical behaviors of a poor-prognosis subset of meningiomas. We carried out proteomic analyses of tissue extracts to discover new markers to accurately distinguish between infiltrative and noninfiltrative meningiomas. METHODOLOGY/PRINCIPAL FINDINGS: Protein lysates of 64 different tissue samples (including two brain-invasive and 32 infiltrative tumors) were submitted to SELDI-TOF mass spectrometric analysis. Mass profiles were used to build up both unsupervised and supervised hierarchical clustering. One marker was found at high levels in noninvasive and noninfiltrative tumors and appeared to be a discriminative marker for clustering infiltrative and/or invasive meningiomas versus noninvasive meningiomas in two distinct subsets. Sensitivity and specificity were 86.7% and 100%, respectively. This marker was purified and identified as a multiphosphorylated form of vimentin, a cytoskeletal protein expressed in meningiomas. CONCLUSIONS/SIGNIFICANCE: Specific forms of vimentin can be surrogate molecular indicators of the invasive/infiltrative phenotype in tumors
Quand la cataracte conduit à une greffe de la cornée
LâĆil possĂšde deux lentilles convergentes disposĂ©es en sĂ©rie : la cornĂ©e et le cristallin. Elles associent leurs puissances. Lâimage qui est naturellement dĂ©focalisĂ©e Ă lâinfini, en les traversant successivement, se focalise sur la rĂ©tine pour ĂȘtre vue nette (Figure
Greffe de cornĂ©e Ă haut risque (IntĂ©rĂȘt de la ciclosporine collyre)
PARIS-BIUM (751062103) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocSudocFranceF
La pachymétrie cornéenne (validité des mesures d'élévation chez des sujets normaux)
PARIS7-Xavier Bichat (751182101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF
Kératoplasties lamellaires antérieures profondes avec profil de découpe en Z réalisé au laser femtoseconde
PARIS7-Xavier Bichat (751182101) / SudocSudocFranceF