Cystic Fibrosis Human Organs-on-a-Chip.

Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane regulator (CFTR) gene: the gene product responsible for transporting chloride and bicarbonate ions through the apical membrane of most epithelial cells. Major clinical features of CF include respiratory failure, pancreatic exocrine insufficiency, and intestinal disease. Many CF animal models have been generated, but some models fail to fully capture the phenotypic manifestations of human CF disease. Other models that better capture the key characteristics of the human CF phenotype are cost prohibitive or require special care to maintain. Important differences have been reported between the pathophysiology seen in human CF patients and in animal models. These limitations present significant limitations to translational research. This review outlines the study of CF using patient-derived organs-on-a-chip to overcome some of these limitations. Recently developed microfluidic-based organs-on-a-chip provide a human experimental model that allows researchers to manipulate environmental factors and mimic in vivo conditions. These chips may be scaled to support pharmaceutical studies and may also be used to study organ systems and human disease. The use of these chips in CF discovery science enables researchers to avoid the barriers inherent in animal models and promote the advancement of personalized medicine.

Secreted Phospholipase A2 Group X Acts as an Adjuvant for Type 2 Inflammation, Leading to an Allergen-Specific Immune Response in the Lung.

Secreted phospholipase A2 (sPLA2) enzymes release free fatty acids, including arachidonic acid, and generate lysophospholipids from phospholipids, including membrane phospholipids from cells and bacteria and surfactant phospholipids. We have shown that an endogenous enzyme sPLA2 group X (sPLA2-X) is elevated in the airways of asthmatics and that mice lacking the sPLA2-X gene (Pla2g10) display attenuated airway hyperresponsiveness, innate and adaptive immune responses, and type 2 cytokine production in a model of airway sensitization and challenge using a complete allergen that induces endogenous adjuvant activity. This complete allergen also induces the expression of sPLA2-X/Pla2g10 In the periphery, an sPLA2 found in bee venom (bee venom PLA2) administered with the incomplete Ag OVA leads to an Ag-specific immune response. In this study, we demonstrate that both bee venom PLA2 and murine sPLA2-X have adjuvant activity, leading to a type 2 immune response in the lung with features of airway hyperresponsiveness and Ag-specific type 2 airway inflammation following peripheral sensitization and subsequent airway challenge with OVA. Further, the adjuvant effects of sPLA2-X that result in the type 2-biased OVA-specific adaptive immune response in the lung were dependent upon the catalytic activity of the enzyme, as a catalytically inactive mutant form of sPLA2-X does not elicit the adaptive component of the immune response, although other components of the immune response were induced by the inactive enzyme, suggesting receptor-mediated effects. Our results demonstrate that exogenous and endogenous sPLA2s play an important role in peripheral sensitization, resulting in airway responses to inhaled Ags.

Secreted PLA2 group X orchestrates innate and adaptive immune responses to inhaled allergen.

Phospholipase A2 (PLA2) enzymes regulate the formation of eicosanoids and lysophospholipids that contribute to allergic airway inflammation. Secreted PLA2 group X (sPLA2-X) was recently found to be increased in the airways of asthmatics and is highly expressed in airway epithelial cells and macrophages. In the current study, we show that allergen exposure increases sPLA2-X in humans and in mice, and that global deletion of Pla2g10 results in a marked reduction in airway hyperresponsiveness (AHR), eosinophil and T cell trafficking to the airways, airway occlusion, generation of type-2 cytokines by antigen-stimulated leukocytes, and antigen-specific immunoglobulins. Further, we found that Pla2g10-/- mice had reduced IL-33 levels in BALF, fewer type-2 innate lymphoid cells (ILC2s) in the lung, less IL-33-induced IL-13 expression in mast cells, and a marked reduction in both the number of newly recruited macrophages and the M2 polarization of these macrophages in the lung. These results indicate that sPLA2-X serves as a central regulator of both innate and adaptive immune response to proteolytic allergen.

Delayed full-thickness macular hole closure without vitreomacular traction release following ocriplasmin injection.

We report a case of a 77-year-old Caucasian woman, treated with ocriplasmin injection for vitreomacular traction (VMT) and full-thickness macular hole (FTMH), who had a persistence outer retinal defect on her 28-day review, without VMT resolution, then presented 3 months later with complete macular hole closure, with persistence of vitreomacular adhesion. This case raises the question on the validity of the 28-day fixed date to assess final outcome of ocriplasmin injection for FTMH associated with VMT, and sheds new lights on the behaviour of the posterior hyaloid in cases of vitreolysis by a chemical agent such as ocriplasmin.

Survey of policy for MRSA screening in English cataract surgical units and changes to practice after updated National guidelines.

BACKGROUND: National guidelines on MRSA (methicillin-resistant Staphylococcus aureus) screening policy in England have changed on a number of occasions, but there is limited data on its influence at a local level. The aim of this study was to determine if changes in National policy influenced preoperative screening of cataract patients for MRSA. METHODS: A structured telephone survey was conducted on all 133 ophthalmology units in England in 2004 and again in 2007 for the initial responders, after a change in national policy. RESULTS: A total of 74 units (56%) responded in 2004 and 71 units (96% of initial respondents) in 2007. In 2004, 57% of units screened for MRSA. They screened groups at high risk of carriage, including patients with previous MRSA (93%) and patients from Nursing homes (21%). Swab sites included the nose (100%), eyes (31%) and perineum (62%). In 2007, there was no significant change in the number of units that screened for MRSA (57% vs 66%; p = 0.118; McNemar test). However, more units screened for MRSA in patients from nursing/residential homes (21% vs 51%; p = 0.004, McNemar test), and in patients who had recent admission to hospital (12% vs 36%; p = 0.003). In the second survey, 3 units (6%) now screened patients who were close relatives of MRSA carriers. CONCLUSION: This survey has highlighted inconsistences in MRSA screening practice of day-case cataract surgery patients across England after 2 major national policy changes. A change in DoH policy only led to more units screening patients for MRSA from high risk groups.

Bilateral foveal cysts secondary to Streptococcus constellatus endocarditis.

Infective endocarditis can be acute or subacute, depending on the virulence of the causative organism. It can also cause loss of vision by a variety of mechanisms, ranging from embolic retinal artery occlusion to endogenous endophthalmitis. We illustrate the first report of foveal cyst formation secondary to infective endocarditis. A 53-year-old man presented to his general practitioner with a variety of constitutional symptoms, but initial laboratory and imaging investigations revealed only mild normocytic anaemia, and he was discharged from further medical care. Four weeks later he developed bilateral visual loss associated with whitish lesions of the superficial retina at both foveae. These later developed into foveal cysts with disruption of the photoreceptor inner segment-outer segment junction and persistent poor visual acuity of 6/60 OU. No retinal haemorrhages or Roth spots were noted. Only after he presented with visual loss did further investigations reveal the underlying diagnosis of streptococcal endocarditis. Ophthalmologists assessing retinal pathology which presents in association with undiagnosed constitutional symptoms are advised to refer such patients promptly for thorough medical investigation, including blood culture and echocardiography where appropriate.

Spontaneous suprachoroidal hemorrhage secondary to thrombolysis for the treatment of myocardial infarction.

Suprachoroidal haemorrhage occurs most commonly as an intraoperative or a postoperative complication of ocular surgery. Spontaneous suprachoroidal haemorrhage is rare. Herein a case is described of spontaneous suprachoroidal haemorrhage in a patient who received recombinant tissue plasminogen activator for the treatment of a myocardial infarction. Systemic thrombolysis may induce spontaneous suprachoroidal haemorrhage. Prompt diagnosis and treatment can improve the likelihood of a favourable visual outcome. To the authors' knowledge, there have been only three previous reports in the literature of spontaneous suprachoroidal haemorrhage secondary to thrombolysis.

Filtering blebs at the site of sutured posterior chamber intraocular lenses.

A 78-year-old man with a traumatic giant retinal tear and phacodonesis had 3-port pars plana vitrectomy (3PPPV), lensectomy, and sutured posterior chamber intraocular lens (IOL) implantation. Two years after surgery, a filtration bleb was noted at 1 of the suture sites. In another case, a 32-year-old man with lens subluxation secondary to Marfan's syndrome had 3PPPV, lensectomy, and sutured posterior chamber IOL implantation. Two months after surgery, a filtration bleb was noted at 1 of the suture sites. Sutured posterior chamber IOL implantation is 1 of the few instances in which there is virtually a full-thickness suture through the sclera. We presume the filtering bleb formed as a direct result of the permanent passage created from the posterior chamber to the subconjunctiva due to presence of the suture. Presence of a filtering bleb can lead to complications including endophthalmitis.