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We report a case of type 2 acute macular neuroretinopathy (AMN) that occurred in an otherwise healthy 22-year-old white woman taking oral contraceptives and consuming large quantities of caffeinated coffee. The patient presented with a teardrop-shaped scotoma just inferior to her central vision in her left eye after a recent and significant increase in coffee consumption. A small extrafoveal retinal lesion was present superior to the fovea on pseudocolor fundus photography. Multimodal retinal imaging demonstrated focal disruption of the inner segment-outer segment junction of the photoreceptors with overlying hyperreflectivity at the level of the outer plexiform layer superior to the fovea, consistent with a diagnosis of type 2 AMN. Oral contraceptive use and high caffeine intake may be risk factors for the development of type 2 AMN.
Assuntos
Macula Lutea , Doenças Retinianas , Síndrome dos Pontos Brancos , Doença Aguda , Adulto , Feminino , Humanos , Macula Lutea/diagnóstico por imagem , Imagem Multimodal , Doenças Retinianas/diagnóstico , Tomografia de Coerência Óptica , Adulto JovemRESUMO
PURPOSE: The purpose of this study was to investigate the effect of systemic antiplatelet agents and anticoagulants on the structural and functional outcomes of eyes with branch retinal vein occlusion (BRVO). METHODS: A retrospective longitudinal cohort study was performed on BRVO patients evaluated at a single tertiary care referral center between 2009 and 2017. Medical records were reviewed for antiplatelet agent and anticoagulant use including aspirin, clopidogrel, warfarin, rivaroxaban, apixaban, or dabigatran prior to BRVO onset. In addition, optical coherence tomography (OCT) parameters, clinical outcomes, and treatment patterns were also recorded. RESULTS: A total of 354 BRVO eyes were identified with a mean follow-up time of 36 months. Antiplatelet or anticoagulant use was associated with presence of cystoid macular edema (CME) at presentation after controlling for potential confounding variables in a multivariate logistic regression. Multivariate regression also revealed an association between foveal hemorrhage at presentation and use of antiplatelet or anticoagulant medications. There were no significant differences in visual acuity or prevalence of CME at the final visit in those with antiplatelet/anticoagulant use compared to those not on these agents. CONCLUSION: Although the use of systemic antiplatelet or anticoagulant agents was associated with increased prevalence of CME and foveal hemorrhage at presentation of BRVO, the use of these medications was not associated with different visual or structural outcomes at the final visit.
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PURPOSE: The etiology of meibomian gland dysfunction (MGD) is incompletely understood, despite being a common ophthalmic condition and an area of unmet medical need. It is characterized by an insufficiency in glandular provision of specialized lipids (meibum) to the tear film and is a major cause of dry eye. Work in the allergic eye disease (AED) mouse model has revealed an immunopathogenic role in MGD causation, now raising interest in the applicability of immunomodulatory therapies. As such, we herein ask whether inhibition of lymphocyte function associated antigen (LFA)-1/intracellular adhesion molecules (ICAM)-1 signaling via topical lifitegrast administration has a therapeutic effect on MGD in AED mice. METHODS: Mice were induced with AED by i.p. injection of ovalbumin (OVA) mixed with alum and pertussis toxin, followed 2 weeks later by once daily topical OVA challenges for 7 days. Mice were treated topically with 5% lifitegrast ophthalmic solution or vehicle (PBS) 30 min prior to challenge. We developed a clinical ranking method to assess MGD severity, and also scored clinical allergy. Conjunctivae and draining lymph nodes were collected for flow cytometry. RESULTS: Topical lifitegrast significantly inhibited clinical MGD severity, which was associated with diminished pathogenic TH17 cell and neutrophil numbers in the conjunctiva. No significant change in conjunctival TH2 cells or eosinophils, and only marginal differences in ocular allergy were observed. CONCLUSIONS: In AED mice, lifitegrast inhibited MGD severity marked by a reduction in select immune populations in the conjunctiva. Our findings warrant future examination of lifitegrast in the treatment of patients with forms of MGD.
Assuntos
Síndromes do Olho Seco , Doenças Palpebrais , Hipersensibilidade , Disfunção da Glândula Tarsal , Animais , Síndromes do Olho Seco/tratamento farmacológico , Humanos , Imunidade , Antígeno-1 Associado à Função Linfocitária , Glândulas Tarsais , Camundongos , Fenilalanina/análogos & derivados , Sulfonas , LágrimasRESUMO
Purpose: This report describes the diagnosis of ocular toxocariasis presenting as endophthalmitis in an adult intravenous drug user. Methods: A case is reported. Results: Fundus imaging showed numerous white opacities obscuring the macula. Toxocara canis serology was reactive with an enzyme immunoassay titer of 1:2 (positive ≥ 1:32). Findings from bacterial and fungal cultures were negative, and vitrectomy cytology revealed no organisms. Postoperatively, serial optical coherence tomography imaging demonstrated a slight decrease in size of an intraretinal hyperreflective lesion in the macula. Conclusions: Owing to a variety of presentations, ocular toxocariasis can be challenging to diagnose. In a patient with a history of intravenous drug use where fungal and bacterial organisms are more common causes of endophthalmitis, it is important to have a wide differential of causative organisms, particularly in the context of negative culture results and a worsening clinical examination.
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Myosins are well characterized molecular motors essential for intracellular transport. MYO19 copurifies with mitochondria, and can be released from mitochondrial membranes by high pH buffer, suggesting that positively-charged residues participate in interactions between MYO19 and mitochondria. The MYO19-specific mitochondria outer membrane association (MyMOMA) domain contains approximately 150 amino acids with a pI approximately 9 and is sufficient for localization to the mitochondrial outer membrane. The minimal sequence and specific residues involved in mitochondrial binding have not been identified. To address this, we generated GFP-MyMOMA truncations, establishing the boundaries for truncations based on sequence homology. We identified an 83-amino acid minimal binding region enriched with basic residues (pI â¼ 10.5). We sequentially replaced basic residues in this region with alanine, identifying residues R882 and K883 as essential for mitochondrial localization. Constructs containing the RK882-883AA mutation primarily localized with the endoplasmic reticulum (ER). To determine if ER-associated mutant MyMOMA domain and mitochondria-associated wild type MyMOMA display differences in kinetics of membrane interaction, we paired FRAP analysis with permeabilization activated reduction in fluorescence (PARF) analysis. Mitochondria-bound and ER-bound MYO19 constructs displayed slow dissociation from their target membrane when assayed by PARF; both constructs displayed exchange within their respective organelle networks. However, ER-bound mutant MYO19 displayed more rapid exchange within the ER network than did mitochondria-bound MYO19. Taken together these data indicate that the MyMOMA domain contains strong membrane-binding activity, and membrane targeting is mediated by a specific, basic region of the MYO19 tail with slow dissociation kinetics appropriate for its role(s) in mitochondrial network dynamics. © 2016 Wiley Periodicals, Inc.
Assuntos
Membranas Mitocondriais/metabolismo , Miosinas/metabolismo , Substituição de Aminoácidos , Retículo Endoplasmático/genética , Retículo Endoplasmático/metabolismo , Células HeLa , Humanos , Mutação de Sentido Incorreto , Miosinas/genética , Domínios Proteicos , Transporte Proteico/fisiologiaRESUMO
Understanding kinetic information is fundamental in understanding biological function. Advanced imaging technologies have fostered the development of kinetic analyses in cells. We have developed Permeabilization Activated Reduction in Fluorescence (PARF) analysis for determination of apparent t1/2 and immobile fraction, describing the dissociation of a protein of interest from intracellular structures. To create conditions where dissociation events are observable, cells expressing a fluorescently-tagged protein are permeabilized with digitonin, diluting the unbound protein into the extracellular media. As the media volume is much larger than the cytosolic volume, the concentration of the unbound pool decreases drastically, shifting the system out of equilibrium, favoring dissociation events. Loss of bound protein is observed as loss of fluorescence from intracellular structures and can be fit to an exponential decay. We compared PARF dissociation kinetics with previously published equilibrium kinetics as determined by FRAP. PARF dissociation rates agreed with the equilibrium-based FRAP analysis predictions of the magnitude of those rates. When used to investigate binding kinetics of a panel of cytoskeletal proteins, PARF analysis revealed that filament stabilization resulted in slower fluorescence loss. Additionally, commonly used "general" F-actin labels display differences in kinetic properties, suggesting that not all fluorescently-tagged actin labels interact with the actin network in the same way. We also observed differential dissociation kinetics for GFP-VASP depending on which cellular structure was being labeled. These results demonstrate that PARF analysis of non-equilibrium systems reveals kinetic information without the infrastructure investment required for other quantitative approaches such as FRAP, photoactivation, or in vitro reconstitution assays. © 2016 Wiley Periodicals, Inc.