Impediments to eye transplantation: Ocular viability following optic-nerve transection or enucleation

Maintenance of ocular viability is one of the major impediments to successful whole-eye transplantation. This review provides a comprehensive understanding of the current literature to help guide future studies in order to overcome this hurdle. A systematic multistage review of published literature was performed. Three specific questions were addressed: (1) Is recovery of visual function following eye transplantation greater in cold-blooded vertebrates when compared with mammals? (2) Is outer retina function following enucleation and reperfusion improved compared with enucleation alone? (3) Following optic-nerve transection, is there a correlation between retinal ganglion cell (RGC) survival and either time after transection or proximity of the transection to the globe? In a majority of the studies performed in the literature, recovery of visual function can occur after whole-eye transplantation in cold-blooded vertebrates. Following enucleation (and reperfusion), outer retinal function is maintained from 4 to 9 h. RGC survival following optic-nerve transection is inversely related to both the time since transection and the proximity of transection to the globe. Lastly, neurotrophins can increase RGC survival following optic-nerve transection. This review of the literature suggests that the use of a donor eye is feasible for whole-eye transplantation.published_or_final_versio

Molecular repair of the brain using self-assembling peptides

The brain is a self-assembled network of connections and tissue. During the assembly process there are many changes, some are minute some are system-wide. The final system-wide change that occurs is when an injured brain blocks regeneration. Until recently self-assembly has never been used to repair injured brain structures. Using the mammalian visual system as a model for functional return of vision, we demonstrated that a designed self-assembling peptide nanofiber scaffold created a permissive environment not only for axons to regenerate through the site of an acute injury, but also to knit the brain tissue together. In experiments using a severed optic tract in the hamster, we showed that regenerated axons reconnected to tarnet tissues with sufficient density to promote functional return of vision, as evidenced by visually elicited orienting behaviour. The peptide nanofiber scaffold not only represents a new nanobiomedical technology for tissue repair and restoration, but also raises the possibility of effective treatment of central nervous system and other tissue or organ trauma.link_to_subscribed_fulltex

Ultrasound-enhanced intrascleral delivery of protein

We aim to investigate ultrasound on enhancing protein penetration into the sclera, a non-invasive method to overcome the first barrier in taking the transscleral route for delivering therapeutics. Rabbit eyes were immersed in a fluorescein isothiocyanate conjugated bovine serum albumin solution. The distances of protein penetration, with and without ultrasound (30s continuous wave, 1MHz, 0.05W/cm 2) applied on the sclera, and at different immersion time intervals (0, 5, 15, 30 and 60min), were measured by examining the cryo-sectioned tissues under fluorescence microscope (≥60 measurements from 3 eyes for each condition). Retina was examined for structural damage by histology. It was found that ultrasound enhances the intrascleral penetration of protein, increasing the diffusivity by 1.6-folds while causing no damage to the retinal tissues. This physical modulation of the sclera is temporary, as evident by the restoration of the diffusional resistance at 15min after ultrasound treatment. The negligible effect of ultrasound-induced convection and the minimal temperature rise (<0.5°C), together with cavitation detected by acoustic emission and a decreased penetration distance at higher ultrasound frequency (30s continuous wave, 3MHz, 0.05W/cm 2), suggest that cavitation is a possible mechanism for increasing the permeability of the sclera for diffusive transport. © 2010 Elsevier B.V.link_to_subscribed_fulltex

Resequencing microarray for detection of human adenoviruses in patients with community-acquired gastroenteritis: A proof-of-concept study

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Temperature and pH effects on biophysical and morphological properties of self-assembling peptide RADA 16-1

It has been found that the self-assembling peptide RADA 16-I forms a β-sheet structure and self-assembles into nanofibers and scaffolds in favor of cell growth, hemostasis and tissue-injury repair. But its biophysical and morphological properties, especially for its β-sheet and self-assembling properties in heat- and pH-denatured eonditions, remain largely unclear. In order to better understand and design nanobiomaterials, we studied the self-assembly behaviors of RADA16-I using CD and atomic force microscopy (AFM) measurements in various pH and heat-denatured conditions. Here, we report that the peptide, when exposed to pH 1.0 and 4.0, was still able to assume a typical β-sheet structure and self-assemble into long nanofiber, although its β-sheet content was dramatically decreased by 10% in a pH 1.0 solution. However, the peptide, when exposed to pH 13.0, drastically lost its β-sheet structure and assembled into different small-sized globular aggregates. Similarly, the peptide, when heat-denatured from 25 to 70°C, was still able to assume a typieal β-sheet structure with 46% content, but self-assembled into small-sized globular aggregates at much higher temperature. Titration experiments showed that the peptide RADA16-I exists in three types of ionic species: acidic (fully protonated peptide), zwitterionic (electrically neutral peptide carrying partial positive and negative charges) and basic (fully deprotonated peptide) species, called 'super ions'. The unordered structure and β-turn of these 'super ions' via hydrogen or ionic bonds, and heat Brownian motion under the above denatured conditions would directly affect the stability of the β-sheet and nanofibers. These results help us in the design of future nanobiomaterials, such as biosensors, based on β-sheets and environmental changes. These results also help understand the pathogenesis of the β-sheet-mediated neuronal diseases such as Alzheimer's disease and the mechanism of hemostasis. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd.link_to_subscribed_fulltex

Resequencing microarray for detection of human adenoviruses in patients with conjunctivitis

Background: Although high-density resequencing microarray is useful for detection and tracking the evolution of viruses associated with respiratory tract infections, no report on using this technology for the detection of viruses in patients with conjunctivitis is available. Objectives: To test if high-density resequencing microarray can be applied to detection of viruses in conjunctival swabs for patients with conjunctivitis. Study design: In this prospective proof-of-concept study, every 4 or 5 bacterial culture-negative conjunctival swab samples were pooled and subject to viral detection using TessArray™ Resequencing Pathogen Microarrays-Flu 3.1 (RPM-Flu-3.1). Results were compared with human adenovirus (HAdV) hexon gene PCR sequencing and viral culture. Results: Thirty-two of the 38 conjunctival swab samples were bacterial culture-negative. Four of the 7 pooled samples were positive for HAdV using RPM-Flu-3.1. Hexon gene PCR sequencing on the 38 original individual samples showed that 3 and 4 samples contained HAdVs species D and B respectively. All the 6 samples that were positive for hexon gene PCR but negative for bacterial culture were also positive by the resequencing microarray. Viral culture was positive for HAdV type 3 in 1 sample, which was also positive by PCR and resequencing microarray. Conclusions: Resequencing microarray is as sensitive as PCR for detection of HAdV in conjunctival swabs. Unlike viral culture and hexon gene PCR sequencing, resequencing microarray was not able to differentiate the type and species of HAdV. Development of microarrays for conjunctivitis can be performed for rapid diagnosis of the viral cause of conjunctivitis. © 2009 Elsevier B.V. All rights reserved.link_to_subscribed_fulltex