Publications by authors named "Rachel L Williams"

36 Publications

Material Characterisation and Stratification of Conjunctival Epithelial Cells on Electrospun Poly(ε-Caprolactone) Fibres Loaded with Decellularised Tissue Matrices.

Pharmaceutics 2021 Feb 28;13(3). Epub 2021 Feb 28.

Department of Eye and Vision Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, L7 8TX, UK.

The conjunctiva, an under-researched yet incredibly important tissue, plays key roles in providing protection to the eye and maintaining homeostasis of its ocular surface. Multiple diseases can impair conjunctival function leading to severe consequences that require surgical intervention. Small conjunctival defects can be repaired relatively easily, but larger defects rely on tissue grafts which generally do not provide adequate healing. A tissue engineering approach involving a biomaterial substrate capable of supporting a stratified epithelium with embedded, mucin-secreting goblet cells offers a potential solution. As a first step, this study aimed to induce stratification of human conjunctival epithelial cells cultured on electrospun scaffolds composed from poly(ε-caprolactone) (PCL) and decellularised tissue matrix (small intestinal submucosa (SIS) or urinary bladder matrix (UBM)) and held at the air/liquid interface. Stratification, up to 5 cell layers, occurred more frequently on scaffolds containing PCL + UBM. Incorporation of these decellularised tissue matrices also impacted material properties, with significant changes occurring to their fibre diameter, tensile properties, and chemical composition throughout the scaffold structure compared to PCL alone. These matrix containing scaffolds warrant further long-term investigation as a potential advanced therapy medicinal product for conjunctiva repair and regeneration.
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http://dx.doi.org/10.3390/pharmaceutics13030318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997349PMC
February 2021

Plasma polymer surface modified expanded polytetrafluoroethylene promotes epithelial monolayer formation in vitro and can be transplanted into the dystrophic rat subretinal space.

J Tissue Eng Regen Med 2021 Jan 23;15(1):49-62. Epub 2020 Nov 23.

Department of Eye and Vision Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK.

The aim of this study was to evaluate whether the surface modification of expanded polytetrafluoroethylene (ePTFE) using an n-heptylamine (HA) plasma polymer would allow for functional epithelial monolayer formation suitable for subretinal transplant into a non-dystrophic rat model. Freshly isolated iris pigment epithelial (IPE) cells from two rat strains (Long Evans [LE] and Dark Agouti [DA]) were seeded onto HA, fibronectin-coated n-heptylamine modified (F-HA) and unmodified ePFTE and fibronectin-coated tissue culture (F-TCPS) substrates. Both F-HA ePTFE and F-TCPS substrates enabled functional monolayer formation with both strains of rat. Without fibronectin coating, only LE IPE formed a monolayer on HA-treated ePTFE. Functional assessment of both IPE strains on F-HA ePTFE demonstrated uptake of POS that increased significantly with time that was greater than control F-TCPS. Surgical optimization using Healon GV and mixtures of Healon GV: phosphate buffered saline (PBS) to induce retinal detachment demonstrated that only Healon GV:PBS allowed F-HA ePTFE substrates to be successfully transplanted into the subretinal space of Royal College of Surgeons rats, where they remained flat beneath the neural retina for up to 4 weeks. No apparent substrate-induced inflammatory response was observed by fundus microscopy or immunohistochemical analysis, indicating the potential of this substrate for future clinical applications.
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http://dx.doi.org/10.1002/term.3154DOI Listing
January 2021

A human retinal microvascular endothelial-pericyte co-culture model to study diabetic retinopathy in vitro.

Exp Eye Res 2020 12 8;201:108293. Epub 2020 Oct 8.

Department of Eye and Vision Science, Institute of Life Course & Medical Sciences, University of Liverpool, William Henry Duncan Building, 6 West Derby St, Liverpool, United Kingdom. Electronic address:

This human primary co-culture model using human retinal microvascular endothelial cells (hREC) and human retinal pericyte cells (hRP) aims to improve current understanding of the cellular changes occurring in the retinal microvasculature during diabetic retinopathy (DR). Currently, patients often present in clinic with late-stage DR, only when vision becomes impaired. Therefore, new strategies for earlier detection in clinic, combined with novel pharmaceutical and cellular interventions are essential in order to slow or halt the progression of DR from background to sight-threatening stage. This co-culture model can be used as a simple, replicable in vitro tool to discover and assess novel drug therapies and improve fundamental understanding of alterations to cell behaviour in the human retinal microvasculature during DR. hRP and hREC were cultured for up to 21 days in normoxic (20%) or hypoxic (2%) oxygen levels and physiological (5.5 mM) or very high (33 mM) glucose, to maintain a healthy, or induce a diabetic-like phenotype in vitro. Mono- or co-cultured hREC and hRP were seeded 1:1 in healthy (20% oxygen and 5.5 mM glucose) or diabetic-like (2% oxygen and 33 mM glucose) conditions, on either side of untreated polyethylene terephthalate (PET) transwell inserts, and cultured for 21 days. Mono- and co-cultures were analysed for changes in metabolic activity, angiogenic response and junctional protein expression, using immunofluorescence antibody labelling, flow cytometry and multiplex ELISA technology. hRP and hREC were successfully co-cultured, and the glucose and oxygen concentrations selected for the in vitro healthy and diabetic-like conditions were sufficient for cell viability and EC monolayer integrity, with evidence of an angiogenic response in diabetic-like conditions within the 21 day timeframe. Angiopoietin-2 (Ang-2), vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF) secretion were all increased, whilst hepatocyte growth factor (hHGF), tissue inhibitor for metalloproteinase-2 (TIMP-2) and interleukin-8 (IL-8) secretion were all reduced in the in vitro diabetic-like conditions. The secretion profile of co-cultures was different to mono-cultures, highlighting the importance of using co-culture models to collect data more reflective of the close relationship between hRP-hREC in vivo. Previous groups have developed useful co-culture models utilising non-human, immortalised or large vessel-sourced cells to explore changes to the vasculature during hypoxia and/or high glucose insult. In this study the use of human primary, retina-specific microvascular cells, mono- and co-cultured, collected over a longer culture period, has enabled detection of changes that may have been missed in previous models.
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http://dx.doi.org/10.1016/j.exer.2020.108293DOI Listing
December 2020

Antimicrobial Activity of Poly-epsilon-lysine Peptide Hydrogels Against Pseudomonas aeruginosa.

Invest Ophthalmol Vis Sci 2020 08;61(10):18

Department of Eye and Vision Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, United Kingdom.

Purpose: To determine the antimicrobial activity of poly-epsilon-lysine (pɛK) functionalization of hydrogels against Pseudomonas aeruginosa.

Methods: Antimicrobial activities of pɛK and pɛK+ hydrogels were tested against both keratitis and a laboratory strain of Paeruginosa at a range of inocula sizes, over 4 and 24 hours. The number of viable CFU on pɛK and pɛK+ hydrogels or commercial contact lenses (CL) was investigated. Ex vivo porcine corneas were inoculated with Paeruginosa PAO1 (103 CFU) and incubated with pɛK+ hydrogels or commercial hydrogel CL for 24 hours and the effects of infection determined.

Results: PɛK+ hydrogels showed log reductions in viable CFU compared with pɛK hydrogels for all Paeruginosa strains, depending on inocula sizes and incubation time. After 24 hours pɛK+ hydrogels showed >5 and >7.5 log reduction in CFU compared with commercial hydrogel CL at 103 and 106 CFU, respectively. In an ex vivo porcine corneal infection model, pɛK+ hydrogels led to a significant decrease in viable PAO1 CFU and histologic analysis indicated a decreased infiltration of PAO1 into the stroma.

Conclusions: PɛK+ hydrogels demonstrated enhanced antimicrobial activity versus nonfunctionalized pɛK hydrogels against clinically relevant Paeruginosa strains. PɛK+ hydrogels have the potential to be used as a bandage CL with innate antimicrobial characteristics to minimize the risk of microbial keratitis.
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http://dx.doi.org/10.1167/iovs.61.10.18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441358PMC
August 2020

Exploratory Use of Fluorescent SmartProbes for the Rapid Detection of Microbial Isolates Causing Corneal Ulcer.

Am J Ophthalmol 2020 11 20;219:341-350. Epub 2020 Jun 20.

Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom. Electronic address:

Purpose: To explore the use of optical SmartProbes for the rapid evaluation of corneal scrapes from patients with suspected microbial keratitis, as a clinical alternative to Gram stain.

Design: Experimental study with evaluation of a diagnostic technology.

Methods: Corneal scrapes were collected from 267 patients presenting with microbial keratitis at a referral cornea clinic in South India. Corneal scrapes were flooded with SmartProbes (BAC One or BAC Two) and evaluated by fluorescence microscopy (without the need for sample washing or further processing). The SmartProbe-labeled samples were scored as bacteria/fungi/none (BAC One) or gram-negative bacteria/none (BAC Two) and compared to Gram stain results.

Results: Compared to Gram stain, BAC One demonstrated sensitivity and specificity of 80.0% and 87.5%, respectively, positive and negative predictive values (PPV, NPV) of 93.8% and 65.1%, and an accuracy of 82.2. BAC Two demonstrated sensitivity and specificity of 93.3% and 84.8%, respectively, an NPV of 99.2%, and an accuracy of 85.6%. When the corresponding culture results were compared to the Gram stain result, the sensitivity and specificity were 73.4% and 70.7%, the PPV and NPVs were 86.5% and 51.0%, and overall accuracy was 72.6.

Conclusions: Fluorescent SmartProbes offer a comparative method to Gram stain for delineating gram-positive or gram-negative bacteria or fungi within corneal scrapes. We demonstrate equivalent or higher sensitivity, specificity, PPV and NPVs, and accuracy than culture to Gram stain. Our approach has scope for point-of-care clinical application to aid in the diagnosis of microbial keratitis.
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http://dx.doi.org/10.1016/j.ajo.2020.06.014DOI Listing
November 2020

Mass Spectrometry Reveals α-2-HS-Glycoprotein as a Key Early Extracellular Matrix Protein for Conjunctival Cells.

Invest Ophthalmol Vis Sci 2020 03;61(3):44

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Purpose: To determine the composition of extracellular matrix (ECM) proteins secreted by a conjunctival epithelial cell line and to identify components that aid conjunctival epithelial cell culture.

Methods: Human conjunctival epithelial cell line (HCjE-Gi) cells were cultured in serum-free media and their ECM isolated using ammonium hydroxide. Growth characteristics were evaluated for fresh HCjE-Gi cells plated onto ECMs obtained from 3- to 28-day cell cultures. Mass spectrometry was used to characterize the ECM composition over 42 culture days. Cell adhesion and growth on pre-adsorbed fibronectin and α-2-HS-glycoprotein (α-2-HS-GP) were investigated.

Results: Day 3 ECM provided the best substrate for cell growth compared to ECM obtained from 5- to 28-day cell cultures. Mass spectrometry identified a predominantly laminin 332 matrix throughout the time course, with progressive changes to matrix composition over time: proportional decreases in matrix-bound growth factors and increases in proteases. Fibronectin and α-2-HS-GP were 5- and 200-fold enriched as a proportion of the early ECM relative to the late ECM, respectively. Experiments on these proteins in isolation demonstrated that fibronectin supported rapid cell adhesion, whereas fibronectin and α-2-HS-GP both supported enhanced cell growth compared to tissue culture polystyrene.

Conclusions: These data reveal α-2-HS-GP as a candidate protein to enhance the growth of conjunctival epithelial cells and raise the possibility of exploiting these findings for targeted improvement to synthetic tissue engineered conjunctival substrates.
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http://dx.doi.org/10.1167/iovs.61.3.44DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401837PMC
March 2020

and computational modelling of drug delivery across the outer blood-retinal barrier.

Interface Focus 2020 Apr 14;10(2):20190132. Epub 2020 Feb 14.

Department of Eye and Vision Science, University of Liverpool, Liverpool, UK.

The ability to produce rapid, cost-effective and human-relevant data has the potential to accelerate the development of new drug delivery systems. Intraocular drug delivery is an area undergoing rapid expansion, due to the increase in sight-threatening diseases linked to increasing age and lifestyle factors. The outer blood-retinal barrier (OBRB) is important in this area of drug delivery, as it separates the eye from the systemic blood flow. This study reports the development of complementary and models to study drug transport from silicone oil across the OBRB. Monolayer cultures of a human retinal pigmented epithelium cell line, ARPE-19, were added to chambers and exposed to a controlled flow to simulate drug clearance across the OBRB. Movement of dextran molecules and release of ibuprofen from silicone oil in this model were measured. Corresponding simulations were developed using COMSOL Multiphysics computational fluid dynamics software and validated using independent datasets. Computational simulations were able to predict dextran movement and ibuprofen release, with all of the features of the experimental release profiles being observed in the simulated data. Simulated values for peak concentrations of permeated dextran and ibuprofen released from silicone oil were within 18% of the results. This model could be used as a predictive tool for drug transport across this important tissue.
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http://dx.doi.org/10.1098/rsfs.2019.0132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7061949PMC
April 2020

Antimicrobial Nitric Oxide Releasing Contact Lens Gels for the Treatment of Microbial Keratitis.

ACS Appl Mater Interfaces 2019 Oct 2;11(41):37491-37501. Epub 2019 Oct 2.

School of Engineering , University of Liverpool , Brownlow Hill , Liverpool L69 3GH , United Kingdom.

Microbial keratitis is a serious sight threatening infection affecting approximately two million individuals worldwide annually. While antibiotic eye drops remain the gold standard treatment for these infections, the significant problems associated with eye drop drug delivery and the alarming rise in antimicrobial resistance has meant that there is an urgent need to develop alternative treatments. In this work, a nitric oxide releasing contact lens gel displaying broad spectrum antimicrobial activity against two of the most common causative pathogens of microbial keratitis is described. The contact lens gel is composed of poly-ε-lysine (pεK) functionalized with nitric oxide (NO) releasing diazeniumdiolate moieties which enables the controlled and sustained release of bactericidal concentrations of NO at physiological pH over a period of 15 h. Diazeniumdiolate functionalization was confirmed by Fourier transform infrared (FTIR), and the concentration of NO released from the gels was determined by chemiluminescence. The bactericidal efficacy of the gels against and was ascertained, and between 1 and 4 log reductions in bacterial populations were observed over 24 h. Additional cell cytotoxicity studies with human corneal epithelial cells (hCE-T) also demonstrated that the contact lens gels were not cytotoxic, suggesting that the developed technology could be a viable alternative treatment for microbial  keratitis.
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http://dx.doi.org/10.1021/acsami.9b13958DOI Listing
October 2019

Poly-ε-lysine based hydrogels as synthetic substrates for the expansion of corneal endothelial cells for transplantation.

J Mater Sci Mater Med 2019 Sep 4;30(9):102. Epub 2019 Sep 4.

Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool, 6 West Derby Street, Liverpool, L7 8TX, UK.

Dysfunction of the corneal endothelium (CE) resulting from progressive cell loss leads to corneal oedema and significant visual impairment. Current treatments rely upon donor allogeneic tissue to replace the damaged CE. A donor cornea shortage necessitates the development of biomaterials, enabling in vitro expansion of corneal endothelial cells (CECs). This study investigated the use of a synthetic peptide hydrogel using poly-ε-lysine (pεK), cross-linked with octanedioic-acid as a potential substrate for CECs expansion and CE grafts. PεK hydrogel properties were optimised to produce a substrate which was thin, transparent, porous and robust. A human corneal endothelial cell line (HCEC-12) attached and grew on pεK hydrogels as confluent monolayers after 7 days, whereas primary porcine CECs (pCECs) detached from the pεK hydrogel. Pre-adsorption of collagen I, collagen IV and fibronectin to the pεK hydrogel increased pCEC adhesion at 24 h and confluent monolayers formed at 7 days. Minimal cell adhesion was observed with pre-adsorbed laminin, chondroitin sulphate or commercial FNC coating mix (fibronectin, collagen and albumin). Functionalisation of the pεK hydrogel with synthetic cell binding peptide H-Gly-Gly-Arg-Gly-Asp-Gly-Gly-OH (RGD) or α2β1 integrin recognition sequence H-Asp-Gly-Glu-Ala-OH (DGEA) resulted in enhanced pCEC adhesion with the RGD peptide only. pCECs grown in culture at 5 weeks on RGD pεK hydrogels showed zonula occludins 1 staining for tight junctions and expression of sodium-potassium adenosine triphosphase, suggesting a functional CE. These results demonstrate the pεK hydrogel can be tailored through covalent binding of RGD to provide a surface for CEC attachment and growth. Thus, providing a synthetic substrate with a therapeutic application for the expansion of allogenic CECs and replacement of damaged CE.
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http://dx.doi.org/10.1007/s10856-019-6303-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6726667PMC
September 2019

Plasma Polymer Coatings To Direct the Differentiation of Mouse Kidney-Derived Stem Cells into Podocyte and Proximal Tubule-like Cells.

ACS Biomater Sci Eng 2019 Jun 17;5(6):2834-2845. Epub 2019 May 17.

Institute of Translational Medicine, University of Liverpool, Crown Street, Liverpool L69 3GE, United Kingdom.

Kidney disease is now recognized as a global health problem and is associated with increased morbidity and mortality, along with high economic costs. To develop new treatments for ameliorating kidney injury and preventing disease progression, there is a need for appropriate renal culture systems for screening novel drugs and investigating the cellular mechanisms underlying renal pathogenesis. There is a need for in vitro culture systems that promote the growth and differentiation of specialized renal cell types. In this work, we have used plasma polymerization technology to generate gradients of chemical functional groups to explore whether specific concentrations of these functional groups can direct the differentiation of mouse kidney-derived stem cells into specialized renal cell types. We found that amine-rich (-NH) allylamine-based plasma-polymerized coatings could promote differentiation into podocyte-like cells, whereas methyl-rich (CH) 1,7-octadiene-based coatings promoted differentiation into proximal tubule-like cells (PTC). Importantly, the PT-like cells generated on the substrates expressed the marker megalin and were able to endocytose albumin, indicating that the cells were functional.
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http://dx.doi.org/10.1021/acsbiomaterials.9b00299DOI Listing
June 2019

Modulated release from implantable ocular silicone oil tamponade drug reservoirs.

J Polym Sci A Polym Chem 2018 04 9;56(8):938-946. Epub 2018 Feb 9.

Department of Eye and Vision Science University of Liverpool Liverpool L7 8TX United Kingdom.

Complicated cases of retinal detachment can be treated with silicone oil tamponades. There is the potential for silicone oil tamponades to have adjunctive drug releasing behaviour within the eye, however the lipophilic nature of silicone oil limits the number of drugs that are suitable, and drug release from the hydrophobic reservoir is uncontrolled. Here, a radiometric technique was developed to accurately measure drug solubility in silicone oil and measure release into culture media. All-trans retinoic acid (atRA), a lipophilic drug known to act as an anti-proliferative within the eye, was used throughout this work. Chain-end modification of polydimethylsiloxane with atRA produced a polydimethylsiloxane retinoate (PDMS-atRA), which was used as an additive to silicone oil to modify the solvent environment within the silicone oil and the distribution coefficient. Blends of PDMS-atRA and silicone oil containing different concentrations of free atRA were produced. The presence of PDMS-atRA in silicone oil had a positive effect on atRA solubility and the longevity of release . The drug release period was independent of atRA starting concentration and dependent on the PDMS-atRA concentration in the blend. A clinically relevant release period of atRA over 7 weeks from a silicone oil blend with PDMS-atRA was observed. © 2018 The Authors. Journal of Polymer Science Part A: Polymer Chemistry Published by Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. , , 938-946.
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http://dx.doi.org/10.1002/pola.28973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5873246PMC
April 2018

Development of a Poly-ε-Lysine Contact Lens as a Drug Delivery Device for the Treatment of Fungal Keratitis.

Invest Ophthalmol Vis Sci 2017 09;58(11):4499-4505

Department of Eye and Vision Science, Institute of Ageing and Chronic Diseases, University of Liverpool, Liverpool, United Kingdom.

Purpose: The purpose of this study was to develop a more efficient drug delivery device to overcome the limitations of current drop therapy for the treatment of fungal keratitis.

Methods: Amphotericin B (AmpB), 0 to 30 μg/mL, was associated with a poly-ε-lysine (pεK) hydrogel. Fungicidal effect against Candida albicans was assessed at 18 and 42 hours by optical density (OD600) and growth on agar. Tear film dilution effect was mimicked by storage of AmpB pεK gels in 3.4 mL sterile PBS for 24 hours prior to fungal incubation. Drug elution over 96 hours was evaluated by HPLC, and drug stability was tested while associated with the gel by OD600 up to 48 hours. Lack of cytotoxicity toward the HCE-T corneal epithelial cell line was assessed over 7 days.

Results: AmpB pεK gels show fungicidal activity in normal conditions (0.057 OD600, SD 0.003, P < 0.005) and in the presence of horse serum (0.048 OD600, SD 0.028 P < 0.005) at 18 hours. The drug release profile was above therapeutic levels (0.188 μg/mL) for up to 72 hours. Tear dilution had no significant effect at higher concentrations of AmpB (3 to 10 μg/mL). AmpB pεK gels were not cytotoxic to the HCE-T cell line.

Conclusions: We demonstrated that AmpB pεK gels confer sustained therapeutic antifungal activity for at least 48 hours without corneal epithelial cell line cytotoxicity, suggesting their potential for in vivo use as an antifungal bandage contact lens. This could avoid the need for intensive topical medication in the treatment of fungal keratitis.
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http://dx.doi.org/10.1167/iovs.17-22301DOI Listing
September 2017

The formation of a functional retinal pigment epithelium occurs on porous polytetrafluoroethylene substrates independently of the surface chemistry.

J Mater Sci Mater Med 2017 Aug 13;28(8):124. Epub 2017 Jul 13.

Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.

Subretinal transplantation of functioning retinal pigment epithelial (RPE) cells may have the potential to preserve or restore vision in patients affected by blinding diseases such as age-related macular degeneration (AMD). One of the critical steps in achieving this is the ability to grow a functioning retinal pigment epithelium, which may need a substrate on which to grow and to aid transplantation. Tailoring the physical and chemical properties of the substrate should help the engineered tissue to function in the long term. The purpose of the study was to determine whether a functioning monolayer of RPE cells could be produced on expanded polytetrafluoroethylene substrates modified by either an ammonia plasma treatment or an n-Heptylamine coating, and whether the difference in surface chemistries altered the extracellular matrix the cells produced. Primary human RPE cells were able to form a functional, cobblestone monolayer on both substrates, but the formation of an extracellular matrix to exhibit a network structure took months, whereas on non-porous substrates with the same surface chemistry, a similar appearance was observed after a few weeks. This study suggests that the surface chemistry of these materials may not be the most critical factor in the development of growth of a functional monolayer of RPE cells as long as the cells can attach and proliferate on the surface. This has important implications in the design of strategies to optimise the clinical outcomes of subretinal transplant procedures.
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http://dx.doi.org/10.1007/s10856-017-5926-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5509835PMC
August 2017

Development of decellularized conjunctiva as a substrate for the ex vivo expansion of conjunctival epithelium.

J Tissue Eng Regen Med 2018 02 12;12(2):e973-e982. Epub 2017 Jun 12.

National Health Service Blood and Transplant Tissue Services, Speke, Liverpool, UK.

This study was performed to develop a method to decellularize human conjunctiva and to characterize the tissue in terms of its deoxyribose nucleic acid (DNA) content, tensile strength, collagen denaturation, basement membrane, extracellular matrix components and its potential to support conjunctival epithelial growth. Human conjunctival tissues were subjected to a decellularization process involving hypotonic detergent and nuclease buffers. Variations in sodium dodecyl sulfate concentration (0.05-0.5%, w/v) were tested to determine the appropriate concentration of detergent buffer. DNA quantification, collagen denaturation, cytotoxicity and tensile strength were investigated. Human conjunctival cell growth by explant culture on the decellularized tissue substrate was assessed after 28 days in culture. Samples were fixed and paraffin embedded for immunohistochemistry including conjunctival epithelial cell markers and extracellular matrix proteins. Conjunctival tissue from 20 eyes of 10 donors (age range 65-92 years) was used. Decellularization of human conjunctiva was achieved to 99% or greater DNA removal (p < 0.001) with absence of nuclear staining. This was reproducible at the lowest concentration of sodium dodecyl sulfate (0.05% w/v). No collagen denaturation (p = 0.74) and no difference in tensile strength parameters was demonstrated following decellularization. No significant difference was noted in the immunolocalization of collagen IV, laminin and fibronectin, or in the appearance of periodic acid-Schiff-stained basement membranes following decellularization. The decellularized tissue did not exhibit any cytotoxicity and explant culture resulted in the growth of stratified conjunctival epithelium. Allogeneic decellularized human conjunctiva can be successfully decellularized using the described protocol. It represents a novel substrate to support the expansion of conjunctival epithelium for ocular surface cellular replacement therapies. Copyright © 2017 John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/term.2419DOI Listing
February 2018

Controlling drug release from non-aqueous environments: Moderating delivery from ocular silicone oil drug reservoirs to combat proliferative vitreoretinopathy.

J Control Release 2016 12 12;244(Pt A):41-51. Epub 2016 Nov 12.

Department of Chemistry, University of Liverpool, Crown Street, L69 7ZD, UK. Electronic address:

In a number of cases of retinal detachment, treatment may require the removal of the vitreous humour within the eye and replacement with silicone oil to aid healing of the retina. The insertion of silicone oil offers the opportunity to also deliver drugs to the inside of the eye; however, drug solubility in silicone oil is poor and release from this hydrophobic drug reservoir is not readily controlled. Here, we have designed a range of statistical graft copolymers that incorporate dimethylsiloxane and ethylene glycol repeat units within the side chains, allowing short chains of oligo(ethylene glycol) to be solubilised within silicone oil and provide hydrogen bond acceptor sites to interact with acid functional drug molecules. Our hypothesis included the potential for such interactions to be able to delay/control drug release and for polymer architecture and composition to play a role in the silicone oil miscibility of the targeted polymers. This strategy has been successfully demonstrated using both ibuprofen and all-trans retinoic acid; drugs with anti-inflammatory and anti-proliferation activity. After the copolymers were shown to be non-toxic to retinal pigment epithelial cells, studies of drug release using radiochemical approaches showed that the presence of 10v/v% of a linear graft copolymer could extend ibuprofen release over three-fold (from 3days to >9days) whilst the release of all-trans retinoic from the silicone oil phase was extended to >72days. These timescales are highly clinically relevant showing the potential to tune drug delivery during the healing process and offer an efficient means to improve patient outcomes.
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http://dx.doi.org/10.1016/j.jconrel.2016.11.010DOI Listing
December 2016

Towards better characterization and quantification of emulsification of silicone oil in vitro.

Acta Ophthalmol 2017 Aug 24;95(5):e385-e392. Epub 2016 Oct 24.

Department of Ophthalmology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, Pokfulam, Hong Kong.

Purpose: Emulsification is related to complications arising from silicone oil (SO) tamponade. Currently, there is no widely accepted method for testing the propensity of SO to emulsify that are physiologically realistic and quantitative.

Methods: We compared different ways of inducing emulsification namely vortex mixing, sonication and homogenization. Silicone oil (SO) emulsification was quantitatively assessed using the Coulter counter and laser light scattering. The in vitro results are compared with the droplet size distribution profile of vitreous clinical washout. Conventional SO was compared with two novel SO blends with high-molecular-weight (HMW) additives (SO and SO ).

Results: Of the three methods for inducing emulsification, homogenization generated the most consistent emulsion samples with the smallest variance. The results from the Coulter counter measurement correlated strongly with the laser light scattering measurement within the range of 1 to 30 µm. The droplet size distribution profiles from human eyes were similar to that of emulsions generated in vitro by homogenization. The human size distribution profile was within the range of values obtained by the in vitro experiment. Compared to the conventional SO, the emulsion droplet counts for the new SO blends were significantly lower (SO and SO were 79% (±17%) and 49% (±18%) of the SO and SO , respectively; p = 0.03 and p = 0.002).

Conclusion: Emulsion generated in vitro by homogenization has similar droplet size profile as human eyes filled with SO. Using this method to induce emulsion, SO blends with HMW additives demonstrated less propensity to emulsification with lower droplet counts compared to conventional SO with similar shear viscosity.
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http://dx.doi.org/10.1111/aos.13258DOI Listing
August 2017

A Novel Peptide Hydrogel for an Antimicrobial Bandage Contact Lens.

Adv Healthc Mater 2016 08 8;5(16):2013-8. Epub 2016 Jun 8.

Institute of Ageing and Chronic Diseases, Department of Eye and Vision Science, University of Liverpool, Apex Building, West Derby Street, Liverpool, L7 8TX, UK.

A peptide hydrogel with an antimicrobial activity is developed as a bandage contact lens. The antimicrobial activity is enhanced with the addition of the biomolecules penicillin G or poly-ε-lysine and is positive against Staphylococcus aureus and Escherichia coli. The lens is also noncytotoxic toward a human corneal epithelial cell line and as a consequence is of great potential as a drug-eluting bandage lens replacing conventional corneal ulcer treatment.
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http://dx.doi.org/10.1002/adhm.201600258DOI Listing
August 2016

Development of emulsification resistant heavier-than-water tamponades using high molecular weight silicone oil polymers.

J Biomater Appl 2015 Aug 11;30(2):212-20. Epub 2015 Mar 11.

Department of Eye and Vision Science, University of Liverpool, Liverpool, United Kingdom.

Purpose: Developing new blends of heavier-than-water silicone oil tamponade agents containing high molecular weight polydimethylsiloxane polymer for use in vitreoretinal surgery.

Materials And Methods: The viscoelastic properties of heavier-than-water silicone oil blends (30.5% F6H8 + 69.5% polydimethylsiloxane) containing high molecular weight polymer additive at increasing concentrations were measured using a controlled-stress rheometer (TA Instruments Rheolyst AR 1000 N). Emulsification of the blends was induced using a sonication device and a pluronic surfactant as a strong emulsifier. The percentage emulsion area was photographed and measured using ImageJ software. In a second in vitro emulsification assessment, silicone oil blends were dispersed using a high shear homogenizer and the oil-in-water droplets were counted using a coulter counter particle analyser.

Results: The addition of the high molecular weight polymer increased shear viscosity and viscoelasticity of the oil blends, which were measureable and to some extent predictable. The in vitro emulsification models produced contradictory results. This demonstrates the difficulty of designing and using in vitro models to evaluate the emulsification tendency of tamponade agents in vivo.

Conclusion: Addition of a high molecular weight polymer to heavy silicone oil can increase the viscoelasticity. These findings might contribute to the development of emulsification resistant heavy silicone oils.
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http://dx.doi.org/10.1177/0885328215575623DOI Listing
August 2015

Fibrinogen adsorption and platelet adhesion to silica surfaces with stochastic nanotopography.

Biointerphases 2014 Dec;9(4):041002

Faculty of Science, University of Technology, Sydney, Broadway, New South Wales 2007, Australia.

In this study, the effect of surface nanoscale roughness on fibrinogen adsorption and platelet adhesion was investigated. Nanorough silica surfaces with a low level of surface roughness (10 nm Rrms) were found to support the same level of fibrinogen adsorption as the planar silica surfaces, while nanorough silica surfaces with higher levels of surface roughness (15 nm Rrms) were found to support significantly less fibrinogen adsorption. All surfaces analyzed were found to support the same level of platelet adhesion; however, platelets were rounded in morphology on the nanorough silica surfaces while platelets were spread with a well-developed actin cytoskeleton on the planar silica. Unique quartz crystal microbalance with dissipation monitoring (QCM-D) responses was observed for the interactions between platelets and each of the surfaces. The QCM-D data indicated that platelets were more weakly attached to the nanorough silica surfaces compared with the planar silica. These data support the role of surface nanotopography in directing platelet-surface interactions even when the adsorbed fibrinogen layer is able to support the same level of platelet adhesion.
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http://dx.doi.org/10.1116/1.4900993DOI Listing
December 2014

Flow behavior of heavy silicone oil during eye movements.

Invest Ophthalmol Vis Sci 2014 Dec 2;55(12):8453-7. Epub 2014 Dec 2.

Department of Ophthalmology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong.

Purpose: Currently there are various heavy silicone oil (HSO) tamponade agents available for treating inferior retinal diseases. Most of these HSO agents are either homogeneous liquids or a mixture of two components. Variations in their emulsification rates in vivo have been reported. In this study, we investigated their flow behaviors during eye-like movements.

Methods: A model eye chamber filled with various HSO agents was driven to perform eye-like movements. Five types of HSOs with different formulations together with 2 other tamponade agents were tested. Movements of various HSOs inside the chamber were captured by video recording and analyzed.

Results: Oxane HD has a larger movement and higher velocity relative to the eye chamber than the less viscous Densiron 68. The behavior of Densiron 68 is similar to that of homogeneous HSO 1.07 and HSO 1.20. Both Oxane HD and 11% silica fluid show very different behaviors compared to the other HSO agents. In addition, 11% silica fluid shows behavior similar to that of F6H8, a low-viscosity tamponade agent.

Conclusions: The viscosity of HSO is not the sole parameter with which to determine the behavior of HSO during eye movements. Various HSOs that are manufactured by mixing different types of base SO and "heavy" additives show distinct flow behaviors. The solubility and stability of the heavy additives in the base SO alter its flow when subjected to eye movements, which may contribute to in vivo emulsification.
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http://dx.doi.org/10.1167/iovs.14-15439DOI Listing
December 2014

Computational fluid dynamic analysis of the effect of morphologic features on distraction forces in fenestrated stent grafts.

J Vasc Surg 2014 Dec 21;60(6):1648-56.e1. Epub 2014 Nov 21.

Liverpool Vascular and Endovascular Service, Royal Liverpool University Hospital, Liverpool, United Kingdom.

Objective: Secure fixation of endovascular stent grafts is essential for successful endovascular aneurysm repair. Hemodynamic distraction forces are generated by blood pressure and blood flow and act against fixation force to encourage migration that may eventually lead to late stent graft failure. The aim of this in silico study was to determine which morphologic features were associated with greater distraction force.

Methods: Computer models of 54 in situ fenestrated stent grafts were constructed from postoperative computed tomography scans by use of image processing software. Computational fluid dynamic analysis was then performed by use of a commercial finite volume solver with boundary conditions representative of peak systole. Distraction force results were obtained for each component of the stent graft. Distraction force was correlated with lumen cross-sectional area (XSA) at the inlet and outlet of components and was compared between groups of components, depending on the magnitude of four predefined angles within the aortoiliac territory that we describe in detail.

Results: Median total resultant distraction force (RDF) acting on the fenestrated proximal bodies was 4.8 N (1.3-15.7 N); bifurcated distal bodies, 5.6N (1.0-8.0 N); and limb extensions, 1.7 N (0.6-8.4N). Inlet XSA exhibited strong, positive correlation with total RDF in proximal body and distal body components (Spearman correlation coefficient ρ, 0.883 and 0.802, respectively). Outlet XSA exhibited a similarly strong, positive correlation with total RDF in limb extension components (ρ, 0.822). Outlet angulation ≥ 45 degrees was associated with greater total RDF in the limb extension components only (P = .004).

Conclusions: For a given blood pressure, XSA was the most important morphologic determinant of total RDF. Angulation within the aorta was not large enough to influence this, whereas iliac angulation affecting outlet angulation of limb extension components was associated with significantly greater total RDF.
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http://dx.doi.org/10.1016/j.jvs.2014.08.077DOI Listing
December 2014

Novel heavy tamponade for vitreoretinal surgery.

Invest Ophthalmol Vis Sci 2013 Nov 5;54(12):7284-92. Epub 2013 Nov 5.

Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, United Kingdom.

Purpose: The aim of this study was to produce a heavy tamponade with a specific gravity greater than 1.06 g/mL that was optically transparent, could be manufactured using simple processing, could be injected using standard clinical equipment, and would have appropriate biocompatibility.

Methods: Aerosil silica was added to a phenyl trimethicone and mixed via a roller, overhead stirring, and ultrasonics. The refractive index, visible absorbance, and shear viscosity were measured. The injectability of the solutions was evaluated using the Accurus Viscous Fluid Injection system. The tamponade efficiency was assessed using a model eye chamber and compared with that of Densiron 68, Oxane HD, and F6H8. The biocompatibility was evaluated in vitro and in vivo in rabbits.

Results: Tamponade agents were produced with specific gravities of 1.10, 1.11, 1.13, and 1.16 g/mL that had good optical clarity. Mixing using overhead stirring was sufficient to produce tamponade agents with shear viscosities in the range 1000 to 5000 mPa·s that were reproducible and stable during storage. The solutions were easier to inject using the Accurus Viscous Fluid Injection system than silicone oil 1000 mPa·s. The 11% silica solution had greater tamponade efficiency than Densiron 68 or Oxane HD. There was no evidence of cytotoxicity in vitro. Silica solution 11% induced cataract earlier than Polydimethylsiloxane 1000 (PDMS 1000). Silica solution 11% and phenyl trimethicone reduced the a-wave value at 1 week after vitrectomy, but recovery was observed at later time points. Silica solution 11% caused inner nuclear layer (INL) nuclei dropdown in inferior retina from 4 weeks postoperation. Polydimethylsiloxane 1000 induced a similar phenomenon in superior retina 12 weeks postoperation.

Conclusions: We have produced a heavy tamponade with good clarity that has appropriate shear viscosity, injectibility, enhanced tamponade efficiency, and biocompatibility similar to that of PDMS 1000.
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http://dx.doi.org/10.1167/iovs.13-11876DOI Listing
November 2013

Using Long-Term Volunteer Records to Examine Dormouse (Muscardinusavellanarius) Nestbox Selection.

PLoS One 2013 27;8(6):e67986. Epub 2013 Jun 27.

School of Natural and Social Sciences, University of Gloucestershire, Cheltenham, United Kingdom.

Within ecology, there are unanswered questions about species-habitat interactions, which could potentially be resolved by a pragmatic analysis of a long-term volunteer-collected dataset. Here, we analysed 18 years of volunteer-collected data from a UK dormouse nestbox monitoring programme to determine the influence of habitat variables on nestbox choice by common dormice (Muscardinusavellanarius). We measured a range of habitat variables in a coppiced woodland in Gloucestershire, UK, and analysed these in relation to dormouse nestbox occupancy records (by dormice, other small mammals, and birds) collected by volunteers. While some characteristics of the woodland had changed over 18 years, simple transformation of the data and interpretation of the results indicated that the dataset was informative. Using stepwise regressions, multiple environmental and ecological factors were found to determine nestbox selection. Distance from the edge of the wood was the most influential (this did not change over 18 years), with boxes in the woodland interior being selected preferentially. There was a significant negative relationship with the presence of ferns (indicative of damp shady conditions). The presence of oak (a long-lived species), and the clumped structural complexity of the canopy were also important factors in the final model. There was no evidence of competition between dormice and birds or other mammals. The results provide greater understanding of artificial dormouse nest-site requirements and indicate that, in terms of habitat selection, long-term volunteer-collected datasets contribute usefully to understanding the requirements of species with an important conservation status.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0067986PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3694881PMC
October 2017

Characterization of the interface between adsorbed fibronectin and human embryonic stem cells.

J R Soc Interface 2013 Jun 3;10(83):20130139. Epub 2013 Apr 3.

Institute of Translational Medicine, University of Liverpool, Liverpool, UK.

The cell-substrate interface plays a key role in the regulation of cell behaviour. Defining the properties of this interface is particularly important for human embryonic stem (hES) cell culture, because changes in this environment can regulate hES cell differentiation. It has been established that fibronectin-coated surfaces can promote the attachment, growth and maintenance of the undifferentiated phenotype of hES cells. We investigated the influence of the surface density of adsorbed fibronectin on hES cell behaviour in defined serum-free culture conditions and demonstrated that only 25 per cent surface saturation was required to maintain attachment, growth and maintenance of the undifferentiated phenotype. The influence of surface-adsorbed fibronectin fragments was compared with whole fibronectin, and it was demonstrated that the 120 kDa fragment central binding domain alone was able to sustain hES cells in an undifferentiated phenotype in a similar fashion to fibronectin. Furthermore, hES cell attachment to both fibronectin and the 120 kDa fragment was mediated by integrin α5β1. However, although a substrate-attached synthetic arginine-glycine-aspartic acid (RGD) peptide alone was able to promote the attachment and spreading of fibroblasts, it was inactive for hES cells, indicating that stem cells have different requirements in order to attach and spread on the central fibronectin RGD-cell-binding domain. This study provides further information on the characteristics of the cell-substrate interface required to control hES cell behaviour in clearly defined serum-free conditions, which are needed for the development of therapeutic applications of hES cells.
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http://dx.doi.org/10.1098/rsif.2013.0139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3645423PMC
June 2013

Guided gingival fibroblast attachment to titanium surfaces: an in vitro study.

J Clin Periodontol 2013 Jan 7;40(1):99-108. Epub 2012 Nov 7.

Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.

Aim: To assess the potential of gingival fibroblasts to attach in a predetermined linear orientation to a nano-topography of aligned fibres on titanium surfaces and determine the ability of such cells to deposit aligned collagen fibre matrix.

Materials And Methods: smooth glass and rough titanium substrates were coated with polytetrafluoroethylene (PTFE) nano-fibres. Ammonia plasma treatment was used to modify the surface chemistry. Human gingival fibroblasts were cultured on substrates and orientation and collagen deposition was assessed.

Results: Straight, unidirectional, parallel PTFE nano-fibres were deposited over the titanium features. By 7 days, the majority of cells were observed to orient to untreated fibres despite the presence of competing titanium surface features. On plasma-treated fibre-coated titanium substrates, cell orientation was mixed. On uncoated substrates, the majority of cells oriented to the titanium surface features. On fibre-coated glass substrates, cells oriented themselves with untreated and plasma-treated fibres and secreted collagen in the same direction after 1 week. On uncoated glass substrates, there was no preferred direction of collagen orientation.

Conclusion: Polytetrafluoroethylene nano-fibres induced cell and collagen orientation. Surface chemistry appeared only to affect cell behaviour at early time points. An implant surface that controls cell orientation may also influence the orientation of collagen, providing improved gingival support.
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http://dx.doi.org/10.1111/jcpe.12025DOI Listing
January 2013

Plasma polymer coatings to aid retinal pigment epithelial growth for transplantation in the treatment of age related macular degeneration.

J Mater Sci Mater Med 2012 Aug 23;23(8):2013-21. Epub 2012 May 23.

Department of Eye and Vision Science, University of Liverpool, Liverpool, UK.

Subretinal transplantation of functioning retinal pigment epithelial (RPE) cells grown on a synthetic substrate is a potential treatment for age-related macular degeneration (AMD), a common cause of irreversible vision loss in developed countries. Plasma polymers give the opportunity to tailor the surface chemistry of the artificial substrate whilst maintaining the bulk properties. In this study, plasma polymers with different functionalities were investigated in terms of their effect on RPE attachment and growth. Plasma polymers of acrylic acid (AC), allyl amine (AM) and allyl alcohol (AL) were fabricated and characterised using X-ray photoelectron spectroscopy (XPS) and water contact angle measurements. Octadiene (OD) hydrocarbon films and tissue culture polystyrene were used as controls. Wettability varied from hydrophobic OD to relatively hydrophilic AC. XPS demonstrated four very different surfaces with the expected functionalities. Attachment, proliferation and morphological examination of an RPE cell line and primary RPE cells were investigated. Both cell types grew on all surfaces, with the exception of OD, although the proliferation rate of primary cells was low. Good epithelial morphology was also demonstrated. Plasma polymerised films show potential as cell carrier surfaces for RPE cells in the treatment of AMD.
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http://dx.doi.org/10.1007/s10856-012-4675-6DOI Listing
August 2012

Emulsification of silicone oil and eye movements.

Invest Ophthalmol Vis Sci 2011 Dec 28;52(13):9721-7. Epub 2011 Dec 28.

Eye Institute, Li Ka Shing Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong.

Purpose: Emulsification is an inherent problem of silicone oil used in vitreoretinal surgery. It has been shown that silicone oil can be made more resistant to emulsification and easier to inject by adding high-molecular-weight components (5% or 10% 423-kDa polydimethylsiloxane [PDMS]) to normal 1000 mPa · s silicone oil. The authors hypothesize that this might also reduce the movement of oil within an eye.

Methods: A model eye chamber made of surface-modified poly(methyl methacrylate) was driven by a computer and a stepper motor to mimic saccadic eye movement. Seven silicone oils with different shear and extensional viscosities were tested. Two sets of eye movements were used: (amplitude 9°, angular velocity 390°/s, duration 50 ms) and (amplitude 90 °, angular velocity 360°/s, duration 300 ms). The movements were captured and analyzed by video recording.

Results: The angular velocity of an oil bubble relative to the eye chamber appears to form an exponential relationship with its shear viscosity. Depending on the thickness of the film of aqueous between the eye wall and the oil bubble, the shear rate was estimated to be between 6 and 14 × 10(4) s(-1). The addition of 10% of 423-kDa PDMS to 1000 mPa · s silicone oil significantly reduced the peak relative velocity compared with the base oil of 1000 mPa · s but not 5000 mPa · s.

Conclusions: The addition of high molecular components to a base oil increases its extensional and shear viscosity. Although the extensional viscosity affected the ease with which the oil could be injected, the results showed that it was the shear viscosity that determined the relative velocity between the oil and the wall of the vitreous cavity, and thus the propensity to emulsify.
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http://dx.doi.org/10.1167/iovs.11-8586DOI Listing
December 2011

Ocular epithelial transplantation: current uses and future potential.

Regen Med 2011 Nov;6(6):767-82

Department of Eye & Vision Science, Institute of Ageing & Chronic Disease, University of Liverpool, Daulby Street, L69 3GA, UK.

Visual loss may be caused by a variety of ocular diseases and places a significant burden on society. Replacing or regenerating epithelial structures in the eye has been demonstrated to recover visual loss in a number of such diseases. Several types of cells (e.g., embryonic stem cells, adult stem/progenitor/differentiated epithelial cells and induced pluripotent cells) have generated much interest and research into their potential in restoring vision in a variety of conditions: from ocular surface disease to age-related macular degeneration. While there has been some success in clinical transplantation of conjunctival and particularly corneal epithelium utilizing ocular stem cells, in particular, from the limbus, the replacement of the retinal pigment epithelium by utilizing stem cell sources has yet to reach the clinic. Advances in our understanding of all of these cell types, their differentiation and subsequent optimization of culture conditions and development of suitable substrates for their transplantation will enable us to overcome current clinical obstacles. This article addresses the current status of knowledge concerning the biology of stem cells, their progeny and the use of differentiated epithelial cells to replace ocular epithelial cells. It will highlight the clinical outcomes to date and their potential for future clinical use.
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http://dx.doi.org/10.2217/rme.11.94DOI Listing
November 2011

The impact of axial length on retinal tamponade for gas, silicone oil, and heavy silicone oil, using an in vitro model.

Graefes Arch Clin Exp Ophthalmol 2011 May 30;249(5):671-5. Epub 2010 Dec 30.

Manchester Royal Eye Hospital, Manchester, M13 9WH, UK.

Background: To investigate whether ocular axial length influences the tamponade efficacy of three commonly used agents: gas, silicone oil, and heavy silicone oil.

Methods: A series of filling experiments was conducted using 19-mm and 25-mm surface-modified spherical model eye chambers to mimic the vitreous cavity. For each agent, tamponade efficacy was assessed across a range of percentage fills, and comparison was made between the two model eye chambers. The behavior of each tamponade agent was quantified by measuring (1) the maximum height of the tamponade bubble, and calculating (2) the arc of retinal contact subtended by the tamponade bubble.

Results: Polynomial regression analysis found no statistically significant difference between the regression models for the different-sized model eye chambers for bubble height or arc of retinal contact subtended. This applied to all of the tamponade agents under investigation.

Conclusions: Across the range of cavity sizes under investigation, no significant difference in tamponade efficacy (as reflected by the measured dimensions of the tamponade bubble) was identified.
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http://dx.doi.org/10.1007/s00417-010-1579-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084431PMC
May 2011

Eu-social science: the role of internet social networks in the collection of bee biodiversity data.

PLoS One 2010 Dec 17;5(12):e14381. Epub 2010 Dec 17.

Department of Natural and Social Sciences, University of Gloucestershire, Cheltenham, United Kingdom.

Background: Monitoring change in species diversity, community composition and phenology is vital to assess the impacts of anthropogenic activity and natural change. However, monitoring by trained scientists is time consuming and expensive.

Methodology/principal Findings: Using social networks, we assess whether it is possible to obtain accurate data on bee distribution across the UK from photographic records submitted by untrained members of the public, and if these data are in sufficient quantity for ecological studies. We used Flickr and Facebook as social networks and Flickr for the storage of photographs and associated data on date, time and location linked to them. Within six weeks, the number of pictures uploaded to the Flickr BeeID group exceeded 200. Geographic coverage was excellent; the distribution of photographs covered most of the British Isles, from the south coast of England to the Highlands of Scotland. However, only 59% of photographs were properly uploaded according to instructions, with vital information such as 'tags' or location information missing from the remainder. Nevertheless, this incorporation of information on location of photographs was much higher than general usage on Flickr (∼13%), indicating the need for dedicated projects to collect spatial ecological data. Furthermore, we found identification of bees is not possible from all photographs, especially those excluding lower abdomen detail. This suggests that giving details regarding specific anatomical features to include on photographs would be useful to maximise success.

Conclusions/significance: The study demonstrates the power of social network sites to generate public interest in a project and details the advantages of using a group within an existing popular social network site over a traditional (specifically-designed) web-based or paper-based submission process. Some advantages include the ability to network with other individuals or groups with similar interests, and thus increasing the size of the dataset and participation in the project.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0014381PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3003702PMC
December 2010