Retinal photo-toxicity & light pollution : interests & contribution of the veterinary ophthalmology

Deux rapports de l’ANSES (Agence Nationale de sécurité sanitaire de l’alimentation, de l’environnement et du travail) ont souligné les risques potentiels que l’exposition à des systèmes d’éclairage utilisant des diodes électroluminescentes (DEL), plus particulièrement parce qu’elles émettent de courtes longueurs d’onde (lumière perçue bleue), pouvait exercer sur les santés humaine, animale et environnementale. Deux dangers ont été identifiés : la phototoxicité rétinienne et la dérégulation de l’horloge biologique (chrono-disruption). L’exposition à une lumière intense entraîne la mort de cellules rétiniennes pouvant conduire à la cécité. L’exposition chronique à des lumières phototoxiques de faible intensité accélère le vieillissement des tissus rétiniens pouvant conduire à des maladies dégénératives telles que la Dégénérescence Maculaire Liée à l’Age (DMLA). Les auteurs de ces rapports ont jugé qu’il serait opportun d’évaluer l’extrapolation à l’homme des résultats obtenus chez l’animal de laboratoire. L’objet de cet article est d’illustrer l’apport que l’ophtalmologie vétérinaire pourrait fournir par des observations cliniques pertinentes chez des animaux de compagnie, considérés comme des animaux-patients, et chez les animaux de rente soumis collectivement à des environnements lumineux imposés par les pratiques d’élevage et considérés, par leur nombre, comme des sentinelles environnementales. Les effets délétères de la lumière sont résumés dans une partie consacrée à l’animal de laboratoire, puis sont décrites les principales méthodes de diagnostic clinique de dysfonctionnements rétiniens, communes à l’ophtalmologie humaine et vétérinaire. À l’évidence, le concept d’unicité de la santé (One health, One medicine) s’applique à cette problématique de pollution lumineuse : les médecines humaine et vétérinaire se doivent de travailler de concert pour une appréciation systémique des relations homme-animal-environnement.Two reports of the French ANSES (Agence Nationale de sécurité sanitaire de l’alimentation, de l’environnement et du travail) highlighted the potential risks of exposure to lighting systems using light-emitting diodes (LED), especially because emitting short wavelengths (blue light), on the human, animal and environmental healthes. Two dangers have been identified: the retinal phototoxicity and the biological circadian rythms deregulation (chrono-disruption). Acute exposure to intense light induces retinal cell death that can lead to blindness. Chronic exposure to low-intensity phototoxic light accelerates the aging process of retinal tissues, that can lead to degenerative diseases such as Age-related Macular Degeneration (AMD). The authors of these reports considered that it would be appropriate to evaluate the extrapolation to humans of the results obtained in laboratory animals. The purpose of this article is to illustrate the contribution that veterinary ophthalmology could provide through relevant clinical observations in companion animals, considered as animal-patients, and in livestock collectively subjected to artificial light creating bright environments imposed by farming practices, considered to be – because of their large numbers - environmental sentinels. The deleterious effects of light are summarized in a section devoted to the laboratory animal and then the main methods of clinical diagnosis of retinal dysfunction, common to human and veterinary ophthalmology, are described. Obviously, the concept of uniqueness of health (One health, One medicine) applies to this problem of light pollution: human and veterinary medicine must work together for a systemic appreciation of human-animal-environment relationships

Effects of triamcinolone acetonide on vessels of the posterior segment of the eye

PURPOSE: This study investigates the effects of triamcinolone acetonide (TA) on retinal endothelial cells in vitro and explores the potential vascular toxic effect of TA injected into the vitreous cavity of rats in vivo. METHODS: Subconfluent endothelial cells were treated with either 0.1 mg/ml or 1 mg/ml TA in 1% ethanol. Control cells were either untreated or exposed to 1% ethanol. Cell viability was evaluated at 24 h, 72 h, and five days using the tetrazolium 3-(4,5-dimethylthiazol-2-yl)-2,5 phenyltetrazolium bromide test (MTT) and lactate dehydrogenase (LDH) assays. Cell proliferation was evaluated by 5-bromo-2-deoxyuridine (BrdU) test. Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling assay (TUNEL assay), annexin-binding, and caspase 3 activation. Caspase-independent cell deaths were investigated by immunohistochemistry using antibodies against apoptosis inducing factor (AIF), cytochrome C, microtubule-associated protein (MAP)-light chain 3 (MAP-LC3), and Leukocyte Elastase Inhibitor/Leukocyte Elastase Inhibitor-derived DNase II (LEI/L-DNase II). In vivo, semithin and ultrathin structure analysis and vascular casts were performed to examine TA-induced changes of the choroidal vasculature. In addition, outer segments phagocytosis assay on primary retinal pigment epithelium (RPE) cells was performed to assess cyclooxygenase (COX-2) and vascular endothelial growth factor (VEGF) mRNAs upregulation with or without TA. RESULTS: The inhibitory effect of TA on cell proliferation could not explain the significant reduction in cell viability. Indeed, TA induced a time-dependent reduction of bovine retinal endothelial cells viability. Annexin-binding positive cells were observed. Cytochrome C was not released from mitochondria. L-DNase II was found translocated to the nucleus, meaning that LEI was changed into L-DNase II. AIF was found nuclearized in some cells. LC3 labeling showed the absence of autophagic vesicles. No autophagy or caspase dependent apoptosis was identified. At 1 mg/ml TA induced necrosis while exposure to lower concentrations for 3 to 5 days induced caspase independent apoptosis involving AIF and LEI/L-DNase II. In vivo, semithin and ultrathin structure analysis and vascular casts revealed that TA mostly affected the choroidal vasculature with a reduction of choroidal thickness and increased the avascular areas of the choriocapillaries. Experiments performed on primary RPE cells showed that TA downregulates the basal expression of COX-2 and VEGF and inhibits the outer segments (OS)-dependent COX-2 induction but not the OS-dependent VEGF induction. CONCLUSIONS: This study demonstrates for the first time that glucocorticoids exert direct toxic effect on endothelial cells through caspase-independent cell death mechanisms. The choroidal changes observed after TA intravitreous injection may have important implications regarding the safety profile of TA use in human eyes

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 polymères, 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'iontophorèse, qui permet d'administrer des principes actifs en intraoculaire sans aucune effraction, et l'électroporation 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

Tolerance of high and low amounts of PLGA microspheres loaded with mineralocorticoid receptor antagonist in retinal target site

Mineralocorticoid receptor (MR)contributes to retinal/choroidal homeostasis. Excess MR activation has been shown to be involved in pathogenesis of central serous chorioretinopathy (CSCR). Systemic administration of MR antagonist (MRA) reduces subretinal fluid and choroidal vasodilation, and improves the visual acuity in CSCR patients. To achieve long term beneficial effects in the eye while avoiding systemic side-effects, we propose the use ofbiodegradable spironolactone-loaded polylactic-co-glycolic acid (PLGA)microspheres (MSs). In this work we have evaluated the ocular tolerance of MSs containing spironolactone in rats’ eyes. As previous step, we have also studied the tolerance of the commercial solution of canrenoate salt, active metabolite of spironolactone. PLGA MSs allowed in vitro sustained release of spironolactone for 30 days. Rat eyes injected with high intravitreous concentration of PLGA MSs (10 mg/mL) unloaded and loaded with spironolactone maintained intact retinal lamination at 1 month. However enhanced glial fibrillary acidic protein immunostaining and activated microglia/macrophages witness retinal stress were observed. ERG also showed impaired photoreceptor function. Intravitreous PLGA MSs concentration of 2 mg/mL unloaded and loaded with spironolactone resulted well tolerated. We observed reduced microglial/macrophage activation in rat retina compared to high concentration of MSs with normal retinal function according to ERG. Spironolactone released from low concentration of MSs was active in the rat retina. Low concentration of spironolactone-loaded PLGA MSs could be a safe therapeutic choice for chorioretinal disorders in which illicit MR activation could be pathogenic

Placental Growth Factor Contributes to Micro-Vascular Abnormalization and Blood-Retinal Barrier Breakdown in Diabetic Retinopathy

OBJECTIVE: There are controversies regarding the pro-angiogenic activity of placental growth factor (PGF) in diabetic retinopathy (DR). For a better understanding of its role on the retina, we have evaluated the effect of a sustained PGF over-expression in rat ocular media, using ciliary muscle electrotransfer (ET) of a plasmid encoding rat PGF-1 (pVAX2-rPGF-1). MATERIALS AND METHODS: pVAX2-rPGF-1 ET in the ciliary muscle (200 V/cm) was achieved in non diabetic and diabetic rat eyes. Control eyes received saline or naked plasmid ET. Clinical follow up was carried out over three months using slit lamp examination and fluorescein angiography. After the control of rPGF-1 expression, PGF-induced effects on retinal vasculature and on the blood-external barrier were evaluated respectively by lectin and occludin staining on flat-mounts. Ocular structures were visualized through histological analysis. RESULTS: After fifteen days of rPGF-1 over-expression in normal eyes, tortuous and dilated capillaries were observed. At one month, microaneurysms and moderate vascular sprouts were detected in mid retinal periphery in vivo and on retinal flat-mounts. At later stages, retinal pigmented epithelial cells demonstrated morphological abnormalities and junction ruptures. In diabetic retinas, PGF expression rose between 2 and 5 months, and, one month after ET, rPGF-1 over-expression induced glial activation and proliferation. CONCLUSION: This is the first demonstration that sustained intraocular PGF production induces vascular and retinal changes similar to those observed in the early stages of diabetic retinopathy. PGF and its receptor Flt-1 may therefore be looked upon as a potential regulatory target at this stage of the disease

Observer les baleines et autres Cétacés en France et en Europe. De Mark Carwardine Delachaux et Niestlé (2017)

Berdugo Polak Marianne. Observer les baleines et autres Cétacés en France et en Europe. De Mark Carwardine Delachaux et Niestlé (2017). In: Bulletin de l'Académie Vétérinaire de France tome 171 n°1, 2018. pp. 60-61

Stratégies antiangiogéniques oculaires innovantes (application à des modèles animaux d'angiogénèse oculaire)

Les néovascularisations oculaires sont responsables de pertes de vision irréversibles dans de nombreuses pathologies oculaires, notamment dans la Dégénérescence Maculaire Liée à l'Age (DMLA). Les traitements existants tentent d'extraire chirurgicalement ou d'inhiber le développement de ces néovaisseaux, mais sont associés à des récidives fréquentes, à des effets indésirables ou à des difficultés d'administration intraoculaire de médicaments. Optimiser ces traitements est un des enjeux majeurs de la recherche ophtalmologique actuelle. Au cours de ce travail de thèse, trois aspects différents de l'optimisation des traitements antiangiogéniques oculaires ont été développésPARIS5-BU-Necker : Fermée (751152101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Des yeux et du regard : proverbes et expressions

Les yeux et le regard participent de façon majeure à notre langage non verbal, avant même l’apparition du verbe. Depuis la Bible jusqu’au langage contemporain, en passant par la mythologie grecque, le théâtre, la littérature ou le langage parlé, une multitude d’expressions et de proverbes mettent en scène l’œil, ce qu’il voit et ce qu’il symbolise. Cet article parcourt les champs sémantiques de l’œil et du regard, leur évolution dans le temps, et leur étonnante richesse. En définitive, une revue de notre humanité

Valorization of Automobile Shredder Residue Using Indirect Gasification

Dual fluidized bed (DFB) gasification offers the possibility to convert solid fuels into a valuable gas, comprised of syngas, and hydrocarbons that can be readily handled in petrochemical units. DFB gasifiers are especially suitable for nonhomogeneous fuels, such as waste fractions. In this work, the possibility to use DFB gasification as a recycling/valorization method of automobile shredder residue is investigated. The gasification tests were carried out in the Chalmers 2–4 MWth gasifier over 4 days. The effects of ash on the gas and tar compositions, as well as on the activity of the bed inventory, were evaluated. The results show that 60% of the total carbon in the fuel can be recovered in the form of a permanent gas, whereby the produced gas contains 12%mol of C2–3 hydrocarbons. The tar levels measured in the produced gas were high, although it was clear that decomposition into monomer-like compounds occurred in the reactor, which resulted in the production of valuable petrochemical compounds, corresponding to 8–9% of the carbon in the feed. Using a higher operating temperature was found to be beneficial in terms of obtaining a higher gas yield, regardless of the level of ash enrichment in the system. The high ash levels in the fuel feed did not negatively affect the technical operation of the fluidized bed. Possible routes of carbon recovery are discussed

Emissions of dioxins and furans during steam gasification of Automotive Shredder residue; experiences from the Chalmers 2–4-MW indirect gasifier

\ua9 2019 Emissions of dioxins and furans during the gasification of Automotive Shredder Residue (ASR) were investigated. The experimental work was carried out in a Dual Fluidized Bed (DFB) system, which consists of a 2–4-MWth gasifier that is fluidized with steam, and an interconnected fluidized bed combustor that is fluidized with air. Two different ASR fractions with higher and lower contents of plastic were tested. Measurements were carried out in the flue gas stream exiting the combustion side of the DFB, as well as in the raw gas stream exiting the gasifier side. A calcium (lime) coat was applied to the flue gas filter to ensure compliance with the emissions regulations regarding the retention of HCl and dioxins. The results showed lower emissions of polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/PCDF) in the flue gas when the raw gas derived from the ASR gasification was combusted, as compared to the direct combustion of ASR. The level of polychlorinated compounds in the flue gas before the lime-coated filter was 0.11 ng/m3N dry gas (I-TEQ) when gasification was used as a pre-step, as compared to 0.27 ng/m3N dry gas (I-TEQ) when the ASR was directly combusted. The raw gas produced by gasification contained very low levels of PCDD/PCDF, whereby the toxicity per kg of ASR was 0.17 ng/kgASR, as compared to 3.44 ng/kgASR after passage through the combustion and cooling sections and 0.34 ng/kgASR at the outlet after the lime-coated filter. A higher content of plastic in the ASR led to an increase in the levels of dioxins and furans in the raw gas, with the highest yield seen for highly chlorinated compounds, while higher temperature in the gasifier is shown to be beneficial in reducing dioxin formation