bluuebunny/crossref_metadata_2025 huggingface dataset:
HLA in Portuguese Systemic Lupus Erythematosus Patients and Their Relation to Clinical Features
Authors: Vasconcelos Carlos , Carvalho Claudia , Leal Bárbara , Pereira Clara , Bettencourt Andreia , Costa Paulo P. , Marinho António , Barbosa Paulo , Almeida Isabel , Farinha Fátima , Mendonça Teresa , Correia João Araujo , Mendonça Denisa , Martins Berta
Published: September 2009

Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease translating the different genetic and environmental factors involved. Polymorphisms at several loci, including the major histocompatibility complex (MHC), have been associated worldwide with SLE, although inconsistencies exist among these studies mainly due to genetic heterogeneity between populations and sample characteristics. The aim of the present study was to investigate in Portuguese SLE the association of HLA‐DRB1 alleles with clinical patterns of the disease and severity. Two hundred eighteen Portuguese patients with SLE—42% of whom had kidney involvement—were studied for HLA‐DRB1. Clinical and laboratory manifestations were correlated with HLA allele frequencies. HLA‐DRB1 * 03 allele frequency was significantly higher in SLE patients—as a whole and as either with or without renal involvement—compared to controls, while HLA‐DRB1 * 09 and DRB1 * 13 allele frequencies were decreased. Regarding the relationship with the presence or absence of specific clinical manifestations, it was only found that HLA‐DRB1 * 08 allele frequency was increased in patients with neurological involvement. No association with the presence or absence of anti‐dsDNA, anti‐sm or antiphospholipid antibodies, or antiphospholipid syndrome, was observed. These results were reproducible when analysis was repeated only with patients with more than 5 years of evolution. As in other populations HLA‐DRB1 * 03 is a susceptibility allele in Portuguese SLE patients, while HLA‐DRB1 * 09 and DRB1 * 13 alleles may be protective alleles, not only for the disease, but for the development of nephritis. No correlations with the different clinical manifestations were found, except with the neurological system.
Modeling Socioeconomic Class in Variationist Sociolinguistics
Authors: Dodsworth Robin
Published: August 2009

Modeling socioeconomic class has been a persistent challenge in the analysis of sociolinguistic variation. While early stratificational models formulated on the basis of socioeconomic indicators such as income, occupation, and area of residence revealed compelling patterns of linguistic variation, they were critiqued for their lack of explanatory power at the interactional level and for their marginalization of those without paid employment. Subsequent models have employed cross‐disciplinary concepts such as the linguistic market, social networks, and communities of practice, prioritizing local social distinctions that are understood to reflect or even constitute abstract structural categories such as ‘working class’ or ‘middle class’. It is argued that a full socioeconomic class paradigm for sociolinguistics would also theorize class at the aggregate level, and to this end, sociological class models may prove useful. Contemporary sociological class analysis at the level of social practice offers additional avenues for interfacing with sociology.
Assembling the Space Economy: Governmentality and Economic Geography
Authors: Prince Russell , Dufty Rae
Published: August 2009

The emergence of a ‘new’ economic geography in recent years has emphasised the ways economic processes are inextricably linked to political, cultural and social processes. This article argues that the Foucauldian governmentality literature has the potential to make a contribution here through its operationalisation of the idea that ‘the economic’emerges as a sphere that is distinct from the political, cultural and social spheres rather than being distinct a priori. Drawing on work at the intersection of economic geography and governmentality, this article shows how governmentality has provided a distinctive perspective on many of the key concepts and processes economic geographers study, including particular spaces like the region, particular actors like the manager, and the processes of globalisation and neoliberalism. It is argued that governmentality analysis reveals how knowledge about these concepts and processes shapes their realisation through informing the rationalised deployment of existing and reinvented technologies and programmes of government. The article concludes by arguing that bringing economic geography and governmentality agendas together in theoretically and methodologically innovative research programmes has benefits for both: for the former further cultivating an appreciation for the particular role of the myriad of actors, knowledges and technologies involved in the formation of economic systems, and for the latter by extending the spatial scope of governmentality analyses that have tended to focus on governmental regimes associated with the spatiality of the nation‐state.
The Geopolitics of Global Energy Security
Authors: Bradshaw Michael J.
Published: August 2009

This study examines the geopolitics of global energy security, defined as the influence of geographical factors, such as the distribution of centres of supply and demand, on state and non‐state actions to ensure adequate, affordable and reliable supplies of energy. The first part of this study describes the geographical dimensions of energy supply and demand and the recent global shift in the location of energy production and demand growth. This shift is the result of increasing demand in emerging markets, such as China and India. At the same time, the centres of production are now focused on the Middle East, Africa and the former Soviet Union. These changes present major geopolitical challenges to the energy importing economies of the ‘developed’ world. The second part of the study analyses three of the major issues that now dominate the literature of global energy security: the US addiction to imported oil, the European Union’s reliance on natural gas imports from Russia, and China’s strategy of ‘going out’ to secure equity oil in Africa. In conclusion, it is suggested that there is a need to rethink the geopolitics of energy security to incorporate the interests of both the energy exporting states and new energy importing states and to incorporate the challenge of climate change.
Impaired Glucose Metabolism and the Exaggerated Blood Pressure Response to Exercise Treadmill Testing in Normotensive Patients
Authors: Papavasileiou Maria V. , Thomopoulos Costas , Antoniou Ilias , Papadimitriou Georgios , Seferou Maria , Makris Thomas K.
Published: August 2009

The authors aimed to investigate the association between glucose metabolism measures and the exaggerated blood pressure response (EXBPR) to exercise testing in normotensive nondiabetic patients. One hundred and forty‐two consecutive patients underwent office blood pressure (BP) measurements, 24‐hour BP monitoring, echocardiography, and treadmill exercise test according to the Bruce protocol. The population was divided into 2 groups according to EXBPR at a submaximal workload level. Furthermore, blood samples were obtained for fasting glucose (FG), fasting insulin (FI), and lipid profile assessment. Measures of insulin resistance (homeostasis model assessment of insulin resistance [HOMA‐IR], quantitative insulin sensitivity check index [QUICKI], and McAuley index) were also estimated, and a standardized oral glucose tolerance test was performed to evaluate glucose levels at 120 minutes (G120). Patients with EXBPR (n=40; 27 men) compared with those without EXBPR (n=102; 66 men) were older by 4±6 years (P<.001). FG, FI, G120, HOMA‐IR, QUICKI, and McAuley index differed in patients with EXBPR compared with those without EXBPR (P<.001 for all). Logistic multivariable regression models revealed that the studied glucose metabolism measures, duration of exercise, and 24‐hour systolic BP remained determinants of EXBPR (P<.05 for all) after adjustment. Impaired glucose measures are significant determinants of EXBPR to exercise testing in normotensive nondiabetic patients, suggesting that impaired glucose metabolism may contribute to adverse cardiovascular prognosis including new‐onset hypertension.
Protective Effects of Angiotensin‐Converting Enzyme Inhibitors in High‐Risk African American Men With Coronary Heart Disease
Authors: Papademetriou Vasilios , Kaoutzanis Christodoulos , Dumas Michael , Pittaras Andreas , Faselis Charles , Kokkinos Peter , Fletcher Ross D.
Published: August 2009

Angiotensin‐converting enzyme (ACE) inhibitors have been extensively used for the treatment of patients with cardiovascular disease, but several concerns have been raised about their efficacy in African American (AA) patients with heart failure, hypertension, and left ventricular hypertrophy. In this study the authors assessed the effect of ACE inhibitors on total and cardiovascular mortality in high‐risk AA patients with angiographically proven coronary artery disease (CAD). This was a retrospective analysis of 810 AA men who underwent diagnostic coronary angiography between 1995 and 2003. All patients had demonstrable CAD and had undergone a complete ischemic workup. Follow‐up was from 3 to 10 years. ACE inhibitors were administered to 237 patients, while the remaining 537 patients were not taking ACE inhibitors. Patients taking ACE inhibitors had significantly more comorbidities (hypertension, diabetes, left ventricular hypertrophy, heart failure, severe CAD) at baseline, compared with patients not taking ACE inhibitors (P<.05 for all comorbidities). Despite the unfavorable baseline profile, patients taking ACE inhibitors had significantly lower mortality from CAD during follow‐up than patients who were not taking ACE inhibitors (P=.006). Stroke mortality rates were similar in both groups. Cox regression analysis showed an 80% higher relative risk in patients not receiving ACE inhibitors. These data indicate a substantial benefit from ACE inhibitor therapy in high‐risk AA patients with CAD.
The Relationship Between Flow‐Mediated Dilatation of the Brachial Artery and Intima‐Media Thickness of the Carotid Artery to Framingham Risk Scores in Older African Americans
Authors: Kwagyan John , Hussein Saifudin , Xu Shichen , Ketete Muluemebet , Maqbool Abid R. , Schneider Robert H. , Randall Otelio S.
Published: August 2009

The objective of this study was to investigate the relationship of flow‐mediated dilatation and intima‐media thickness (IMT) with coronary risk in African Americans (AAs). Endothelial dysfunction and IMT of carotid arteries are considered early steps in atherosclerotic disease process and have been used as surrogate markers of subclinical atherosclerosis. Data were collected on 106 AAs with a mean age of 64.0±6.6 years. Carotid artery IMT was measured with B‐mode ultrasonography, as was brachial artery diameter at rest, during reactive hyperemia, and after nitroglycerin. Percent change in flow‐mediated dilatation (%FMD) was defined as 100×(diameter during reactive hyperemia – resting diameter)/resting diameter. Percent change in nitroglycerin‐mediated dilatation (%NMD) was defined as 100×(diameter with nitroglycerin‐resting diameter)/resting diameter. The Framingham 10‐year risk score (FRS) was calculated for each patient using the National Cholesterol Education Program (NCEP) risk score calculator and participants were categorized into 3 groups with FRS as <10%, 10% to 20%, and >20%. Thirty‐eight participants had risk scores <10%, 26 had 10% to 20%, and 42 >20%. There was a significant inverse relation between %FMD and FRS (P<.0001) and between %NMD and FRS (P<.001). IMT was not statistically different among the risk groups. Endothelial dysfunction assessed by FMD significantly correlates inversely with FRS in AAs. FMD, an index of arterial compliance, appears to be a sensitive and reliable index of cardiovascular disease.
Definition and Classification of Hypertension: An Update
Authors: Giles Thomas D. , Materson Barry J. , Cohn Jay N. , Kostis John B.
Published: August 2009

Since the publication of a paper by the American Society of Hypertension, Inc. Writing Group in 2003, some refinements have occurred in the definition of hypertension. Blood pressure is now recognized as a biomarker for hypertension, and a distinction is made between the various stages of hypertension and global cardiovascular risk. This paper discusses the logic underlying the refinements in the definition of hypertension.
Pathogenesis and Treatment of Microalbuminuria in Patients With Diabetes: The Road Ahead
Authors: Kalaitzidis Rigas , Bakris George
Published: August 2009

The incidence of type 2 diabetes is increasing in the United States, which is expected to result in an increased prevalence of microalbuminuria and higher cardiovascular risk. Microalbuminuria is an indication that a low‐level inflammatory process is ongoing. In patients with hypertension, with or without diabetes, increasing urinary albumin excretion (UAE) is associated with elevated levels of inflammatory markers, endothelial dysfunction, and platelet activation. Microalbuminuria is associated with an increased incidence of cardiovascular disease (CVD) morbidity and mortality in patients with hypertension and in those with diabetes with or without hypertension. Antihypertensive agents that modulate the renin‐angiotensin‐aldosterone system (RAAS) can delay the onset and reduce progression of microalbuminuria and decrease CVD morbidity and mortality in patients with diabetes. Clinical trials provide a spectrum of results regarding the protective effects of RAAS‐blocking agents. Consideration of baseline blood pressure (BP), UAE and CVD risk, and the extent of BP lowering with treatment is necessary when interpreting clinical trial results in patients with microalbuminuria. It remains to be determined whether targeting the underlying inflammatory process can retard or prevent microalbuminuria progression or whether treatment of microalbuminuria can prevent end‐stage renal disease or death.
Challenge and Urgency in Defining Doctoral Education in Marriage and Family Therapy: Valuing Complementary Models
Authors: Wampler Karen S.
Published: August 2009

In this overview, I comment on the strong theme of the need to define and improve the quality of doctoral education in marriage and family therapy that pervades the three essays. Deficits in research training are the central concern, although the essayists take different perspectives on the nature of the research training needed. The different perspectives can be understood in terms of three different models of doctoral education. The institutional model focuses on professional training with little financial support for students and lower expectations for faculty research. The community of scholars model emphasizes a balance of research and practice with students required to attend full‐time and financial support provided. Research is a mix of faculty‐ and student‐driven and is often focused on professional issues. The star researcher model often held out as the ideal, although not yet represented in marital and family therapy (MFT), emphasizes faculty externally funded programmatic research with students working on and supported by faculty grant funding. The value and role of all three models in MFT doctoral education are described and discussed.
Principles of immunosuppression in uveitis
Authors: WILLERMAIN F , CASPERS L
Published: September 2009

Non infectious uveitis is a heterogeneous group of diseases mediated through autoimmune and autoinflammatory mechanisms. It is thus crucial to perform a complete work‐up to characterise the disease and eventually find a precise aetiology or a systemic associated condition. When the inflammation is bilateral and the vision threatened, systemic drugs are usually proposed. Despite tremendous progress in the understanding of the disease, treatments are generally based on the administration of non specific immunosuppressive molecules. Currently, high doses oral corticosteroids are first given, followed by a slow tapering of the dosage. If this strategy does not lead to disease control, a steroid‐sparing agent should be considered. Antimetabolites, T‐cell inhibitor and alkylating agents will be chosen (alone or in combination), depending on the severity of the disease and patients general status. Recently the development of biologic agents offers the possibility to target various specific molecules important in non infectious uveitis development. Nowadays, anti‐TNFα have been mostly tested with encouraging results. However, it is likely that different uveitis subtypes would require different biologic agents. In the future, the growing production of specific inhibitors might lead to a more tailored approach of uveitis treatment.
The future in immunomodulation
Authors: DE SMET M
Published: September 2009

Abstract not provided
Tips and tricks for writing a manuscript
Authors: DAMATO B
Published: September 2009

Purpose The aims of this presentation are to highlight some pearls and pitfalls in writing scientific articles.

Methods It is not possible to write a good manuscript unless you have a good message to share. If you are reporting research results this means that you will need to have conducted the research properly, with good statistics, measures to avoid bias, complete data and, of course, an important hypothesis to test. If possible, expert advice should be obtained before the study is started so as to ensure that the trial design is appropriate and that the statistics are correct.

Results The key to writing a good manuscript is to divide the paper into sections and to sub‐divide each section into components, making sure that the sequence of ideas is in the correct order. The internet is full of good advice on how to write a good manuscript. This information be summarized in this presentation, which will also guide participants to useful sources of information.

Conclusion Writing a manuscript is not difficult and should be a pleasurable and rewarding experience as long as one follows a few simple rules, which will be discussed in this talk.
Infectious crystalline keratopathy
Authors: DUA HS
Published: September 2009

Purpose To provide the definition, clinical features, diagnosis and management of infectious crystalline keratopathy (ICK).

Methods Personal experience, experimental study on ex‐vivo ICK and literature review

Results ICK can be defined as microbial infection of the cornea in the absence of the host immune response. It can be caused by a variety of microbes including bacteria and fungi. It is characterised by corneal infiltrates in the form of branching or arborescent patterns of needles, snowflakes or fern shapes. This pattern is determined by the compactness of the corneal lamellae. Clinically there is minimal host inflammatory response although there can be areas of suppuration remote from the ICK. The epithelium is usually intact, symptoms are mild and it runs a chronic indolent course. Corneal hypoesthesia and corticosteroid use are risk factors. Diagnosis is based upon clinical examination in conjunction with careful history taking. The presence of branching crystalline deposits located in the stroma often near suture sites and following corneal surgery should raise suspicion. Intensive topical antibiotics, keratectomy of the affected site to excise lesion if possible, cessation of steroid medication or repeat corneal graft are aspects of management of ICK.

Conclusion ICK is a rare but difficult to treat condition. Diagnosis is based on history and clinical features. Sample (scrape) or biopsy can be taken for culture and sensitivity of organisms involved. Treatment is difficult and surgery may be required to eliminate the infected locus.

Commercial interest
Herpes and zoster keratitis
Authors: BOURCIER T
Published: September 2009

Abstract not provided
Glaucoma and retina
Authors: BRON AM
Published: September 2009

Purpose Retinal and vitreoretinal surgeries frequently lead to an elevation of intraocular pressure (IOP) and/or glaucoma. Clinical presentations correspond to secondary glaucomas with an open‐angle or with angle‐closure.

Results Since myopia is a risk factor for retinal detachment and glaucoma as well, it is not surprising that these two disorders are often combined. Cortiscosteroids are widely used in retinal surgeries and the elevation of IOP related to the use of corticosteroids has long been recognized, whatever the route, topical, intravenous or intravitreal. Specific conditions such as Schwartz syndrome or Ghost‐cell glaucoma are not very frequent. However scleral buckling procedures, injection of air, expansive gas and silicone oil may lead to severe elevations of IOP.

Conclusion The management of these secondary glaucomas can be difficult because of the inflammatory status of the eye and the recurrence of the retinal diseases. Clinical examination and particularly gonioscopy is the key issue to lead the clinician to the appropriate treatment.
Management of retinal tumours
Authors: DESJARDINS L
Published: September 2009

Purpose To describe the clinical presentation, main diagnostic tools, differential diagnostic and managment of retinoblastoma.

Methods Diagnostic modalities include fundus exam under general anesthesia with fundus pictures, ultrasonography and MRI. The more frequent differential diagnosis are coats disease and PHPV. Diffuse infiltrating retinoblastoma can be very difficult to identify An overview of the different therapeutic modalities of retinoblastoma with their specific indications and guidelines for follow up of patients and genetic counseling will be given.

Results Unilateral massive retinoblastoma with no vision left is usually treated by enucleation while most bilateral retinoblastoma and 20% of unilateral can be treated by various conservative techniques including chemotherapy and chemothermotherapy, cryotherapy, plaque brachytherapy and external beam radiotherapy.

Conclusion Early diagnosis of retinoblastoma is still the most important prognostic factor examination of the fundus is warranted in all children with leucokoria and/or strabismus.
Management of conjunctival tumours
Authors: MIDENA E
Published: September 2009

Abstract not provided
The correlation between central corneal thickness, ocular and general parameters
Authors: GALGAUSKAS S , GARLAITE O , JUODKAITE G , TUTKUVIENE J , ASOKLIS R
Published: September 2009

Purpose To evaluate central corneal thickness (CCT) of normal Lithuanian population,to describe the relationship between CCT, height,weight, body mass index (BMI), intraocular pressure (IOP),refraction ability.

Methods In a pilot study 259 adults‐ 125 men and 134 women, whose age ranged in 18‐68 years, were studied. Height, weight and body mass index was determined using a standardized protocol. Non‐cycloplegic refraction was determined by an autorefractor (KR‐8100P, TOPCON). The intraocular pressure was measured by applanation tonometer (Reichert Tono‐pen XL), CCT was measured by contact ultrasound pachymeter (Pocket Pachymeter, Quantel Medical, CP), respectively. Statistical analysis was made using SPSS 17.0 software.Correlations between groups were determined using Pearson two sided correlation coefficient.

Results The mean CCT of males was 549.0 (± 33.6) µm for the right eye (OD) and 549.9 (± 33.8) µm for the left eye (OS). The mean CCT of females was 542.6 (± 34.9) µm for OD and 543.1 (± 35.2) µm for OS. Mean height of the examined persons was 173,06 (± 8,27) cm; mean weight – 68,69 (± 11,84) kg; mean value of the body mass index – 22,83 (± 2,95); mean intraocular pressure – 16,07 (± 2,74) mmHg; mean refraction ability – ‐1,56 (± 2,21) D. Pearson two sided correlation coefficient between CCT and subjects’ age was 0,00; CCT and height – 0,108; CCT and weight – 0,093; CCT and BMI – 0,05; CCT and IOP – 0,26; CCT and refraction – 0,047.

Conclusion 1.No significant difference in mean CCT was found between the right and left eyes or between male and female subjects. 2. CCT correlated with height, weight and IOP; but not BMI or refraction ability in the overall study group. 3.CCT significantly correlated with height.
Changes in expression of matrix metalloproteinases 1 and 8 in corneal epithelial cells after UV irradiation
Authors: ARDAN T , CEJKOVA J
Published: September 2009

Purpose Matrix metalloproteinases 1 and 8 (MMP‐1 and MMP‐8) are collagenolytic enzymes that are associated with many ocular inflammatory diseases, such as uveitis, ulcerative keratitis, and ocular rosacea. It is suggested, that MMP‐1 and MMP‐8 are mainly produced by inflammatory cells so that an increased incidence of these enzymes in the cornea is associated with neutrophil infiltration. Based on our previous findings dealing with the coincidence of the expression of proteolytic enzymes (MMP‐2 and MMP‐9) with the severity of corneal injury induced by UV irradiation, the aim of this study was to investigate the effect of UVA and UVB rays on expression of MMP‐1 and MMP‐8 in the corneal epithelium.

Methods In the first group of rabbits the corneas were irradiated with UVA lamp (365 nm, once a day during 4 days, a dose per day 1.01 J/cm2), in the second group with UVB lamp (312 nm, once a day during 4 days, a dose per day 1.01 J/cm2). Normal corneas served as controls. MMP‐1 and MMP‐8 were examined in cryostat sections immunohistochemically using sheep polyclonal anti‐MMP‐1 and mouse monoclonal anti‐MMP‐8 antibodies.

Results Results show that UVA rays do not change expression of MMPs studied in corneal epithelium. In contrast, UVB rays induce overexpression of both MMPs in corneal epithelial cells.

Conclusion Comparing the effect of the same doses of UVA and UVB rays with the normal cornea, where the enzymes are only slightly (MMP‐1) or moderately (MMP‐8) pronounced in the epithelium, UVB rays (not UVA rays) evoked highly increased expression of both MMPs in irradiated corneal epithelial cells. The possible influence of overexpression of MMPs due to UVB‐exposure on the development of corneal inflammation will be the aim of our next study.
The influence of pollen proteases on human conjunctival cells
Authors: RABENSTEINER DF , SCHMUT O , SPREITZHOFER EM , TRUMMER G , WACHSWENDER C , KIRCHENGAST S , WEDRICH A
Published: September 2009

Purpose During pollen‐seasons allergy‐like symptoms can also be observed in proven non allergy sufferers. Pollen proteases are thought to be responsible for consecutive conjunctival irritation. We investigated the influence of a well known aggressive pollen species, birch pollen (Betula pendula) on human conjunctival cell cultures. This study is an approach to SNAC (seasonal non allergic conjunctivitis) syndrome.

Methods Human cultivated conjunctival cells, so called CHANG‐cells, were incubated with extracts of birch pollen. Zymography was carried out in order to investigate the proteolytic activity of the pollen. Cytomorphological changes were analysed using the CASY1 Cell Counter. Via MTS‐assay the cell viability was quantified. The viability of the cells, which were incubated with pollen extract, was compared to the viability of the control cells and the results were statistically evaluated.

Results Depending on the pollen extract concentration and the incubation period, the treatment of CHANG‐cells with pollen extract of birch induced a highly significant decrease of the cell viability.

Conclusion Cell damage by pollen proteases is an approach to explain conjunctival irritation in proven non‐allergic persons during the pollen season. A reason why not all persons are affected by the SNAC syndrome at the same extent, could be differences in the concentrations of antiproteases present on the ocular surface.
Cirrus HD OCT algorithms for macula and retinal nerve fiber analysis
Authors: HORNE M
Published: September 2009

Abstract not provided
High‐definition Fourier domain OCT: non‐invasive assessment of BRB changes
Authors: BERNARDES R , SANTOS T , CUNHA‐VAZ J
Published: September 2009

Purpose To demonstrate the possibility of using a non‐invasive imaging technique, the high‐definition spectral domain optical coherence tomography, as a surrogate detector of blood‐retinal barrier (BRB) breakdown.

Methods Healthy volunteers and diabetic patients with diabetic retinopathy, age‐ related macular degeneration, choroidal neo‐vascularisation and cystoid macular edema, underwent optical coherence tomography by Cirrus HD‐OCT (Carl Zeiss Meditec, Dublin, CA, USA). Profiles of reflectivity distribution between the inner‐limiting membrane and the retinal pigment epithelium were built, normalized, aligned and compared. Patients underwent retinal leakage analyzer (RLA) to identify areas of retinal fluorescein leakage into the vitreous as areas of blood‐retinal barrier breakdown.

Results The comparison between healthy volunteers’ and patients’ reflectivity distribution demonstrates these profiles differ. Moreover, when comparing reflectivity distribution within the same eye between areas of leakage and areas of non‐leakage, the sum of the squared differences is over one decade relatively to the comparison between two similar areas (leakage/leakage or non‐leakage/non‐leakage).

Conclusion These findings suggest that high‐definition OCT may be useful in identifying areas of retinal leakage/BRB breakdown and therefore to be used as surrogate for fluorescein angiography and retinal leakage analyzer.
Stem cell applications for retinal pigment epithelial cell defects
Authors: SKOTTMAN H
Published: September 2009

Purpose The experimental data on the retinal pigment epithelium (RPE) transplantation clearly show the potential of the cell therapy treatment strategy for RPE dysfunction. Human embryonic stem cells (hESC) may have a significant role as tools for drug discovery and for replacement of damaged cells. Human ESCs are potent origin for mass production of specific cells, thus providing unlimited opportunities for these strategies. However, the utilization of hESC‐derived RPE cells in therapy requires an efficient and xeno‐free differentiation protocol that follows good manufacturing practice (GMP) standards. In addition, it is essential to develop methods for reliable characterization of the cells to gain safe and clinically eligible cells.

Methods We have compared the differentiation potential of several hESC lines and induced RPE differentiation in the absence of animal feeder cells and bovine serum. The differentiation of cells has been followed by expression analysis of retinal cell markers by using qRT‐PCR and protein analysis.

Results With our differentiation protocol, we were able to generate RPE cells from several hESC lines with satisfying efficiency. The typical pigmented cobblestone‐like morphology and expression of retinal precursor markers were detected within one week. Further, RPE specific markers were up‐regulated during the maturation of the cells.

Conclusion We have developed progressive differentiation protocol, which enables generation of RPE cells without animal feeder cells and serum induction. The generated cell material is of high quality and more compatible with GMP requirements than cells generated in previous studies. In my presentation, I will review some of the data using hESC for RPE production and our experience in utilizing the hESC‐derived RPE cells.
Biomaterials for RPE tissue engineering and cell microencapsulation
Authors: URTTI A
Published: September 2009

Abstract not provided
The distribution of neuroglobin in mouse eye
Authors: YOU Y , DEWILDE S , VAN DE VEIRE S , VAN BERGEN T , VANDEWALLE E , MOONS L , MOENS L , STALMANS I
Published: September 2009

Purpose To determine the distribution of neuroglobin (Ngb) in mouse eye. Ngb is predominantly expressed in the nervous system,and at particularly high levels in the retina. Ngb may serve as a reactive oxygen scavenger and may protect the tissue of eye from ischemia/hypoxia injuries. However,the distribution of Ngb in the eye is still controversial.

Methods Two polyclonal antibodies against Ngb were used in this immunohistochemical study, both of which were raised in rabbits. One of these two antibodies was generated against the whole recombinant protein of mouse Ngb and the other was generated against amino acid positions 55‐70 of mouse and human Ngb. The expression of Ngb was analyzed with light microscopy on tissue sections.

Results These two antibodies showed comparable results. Ngb was expressed in the layers of the retina, including the ganglion cell layer, inner and outer nuclear layers, inner and outer plexiform layers, the inner segments of the photoreceptors and the retinal pigment epithelium. Ngb was also detected in other structures of the eye, including the epithelium and endothelium of cornea,the stroma of iris,the ciliary body, the lens epithelium, and the sclera. However, Ngb was not expressed in the corneal stroma, the lens capsule, the lamellar fibers of lens, the pigment epithelium of ciliary body or the pigment layer of iris.

Conclusion Ngb was found widely distributed in mouse eye. This finding can be explained by the fact that most of the structures of the eye originated from neural crest/neural ectoderm. Future experiments will focus on the distribution of Ngb at the mRNA level (in situ hybridization),and the quantitative expression levels at baseline and after hypoxic/ischemic challenge.
Why do we need a biomechanical approach to the ocular rigidity concept?
Authors: KOTLIAR KE , KOSHITS IN , BAUER S , LOHMANN CP , LANZL IM
Published: September 2009

Ocular rigidity in ophthalmology is generally assumed to be a measurable surrogate parameter related to the biomechanical properties of the whole globe. Clinical tonometry and tonography, as well as recently developed methods to assess the ocular pulse amplitude and pulsatile ocular blood flow and measurements with the ocular response analyzer are based on the concept of ocular rigidity. Clinical concepts of ocular rigidity describe a resulting effect without considerations of possible diverse morphology and material properties of the different ocular tissues. It is commonly accepted that ocular rigidity is related to the elasticity of the sclera. Many formulations are however dependent on the internal volume of the globe, intraocular pressure, corneal biomechanics and thickness of the corneoscleral shell. Sometimes this is extended to biomechanical properties of the ocular vasculature and perfusion pressure. Therefore ocular rigidity is expressed in various units and has different physical meanings but the same name is used which is confusing. Ocular biomechanics introduces parameters of elasticity and viscoelasticity of the sclera, cornea and other tissues which consider the morphology of the different tissues describing their mechanical properties such as: Young’s modules of the sclera and Poisson’s ratios of the cornea. When applying these rigorous statements and methods of biomechanical modeling a unified concept for ocular rigidity can be developed in order to link the limited clinical concepts, to improve them and to better understand the results of clinical measurements.
Prospective evaluation of the Boston keratoprosthesis
Authors: AMENT JD , PINEDA R , TILAHUN Y , BEHLAU I , DOHLMAN CH
Published: September 2009

Purpose To assess the sustainability of the Type I Boston Keratoprosthesis in the developing world and report 18‐month follow‐up data on the International Boston Keratoprosthesis Study Group pilot project in Ethiopian.

Methods Through an international collaboration between the Massachusetts Eye and Ear Infirmary, USA and the Menelick II Hospital, Ethiopia, six pre‐selected patients underwent surgery with th Type I Boston Keratoprosthesis (KPro). Patient inclusion criteria included hospital access, multiple graft failure, or binocular blindness. An International Protocol was developed to standardize evaluation and follow‐up. To reduce costs, the patient’s own cornea was used as a carrier for the KPro when possible instead of a donor cornea. Follow‐up reports were transmitted electronically to all physicians involved.

Results Six Ethiopian patients received a Boston KPro under local anesthesia without complications. In two patients, their own cornea was used as a carrier for the KPro. All patients had improved visual acuity from a baseline vision of hand motions. Postoperative vision ranged from CF at 5m to 20/40. All patients were able to self‐administer their ophthalmic medications and five of six patients reported greater independence in ADLs. There were no infections, or compliance issues.

Conclusion Early results indicate that the Boston KPro may be an option in the developing world. KPro complication rates were no different from developed countries. The use of the patient’s own cornea was not associated with a poor outcome. It remains unclear as to whether KPro may be superior to PK in this setting. Careful patient selection, standardized protocol implementation, and meticulous post‐operative follow‐up are necessary for long‐term sustainability.
Boston keratoprosthesis with titanium back plate
Authors: DOHLMAN CH , TODANI A , AMENT JD , CHODOSH J , CIOLINO J , COLBY K , PINEDA R , BELIN M , AQUAVELLA J , GRANEY J
Published: September 2009

Purpose Following implantation of a Boston Keratoprosthesis (BKPro), formation of a retroprosthetic membrane (RPM) is an indication of postoperative intraocular inflammation. The purpose of this retroactive study has been to compare BKPro back plates made of titanium with the standard PMMA back plates. Any difference in RPM formation would guide our future choice of material for the device.

Methods The design was a retroactive analysis looking at the surgical outcomes after 6 months in patients who had BKPro implants. Pediatric cases were excluded. The indications for having a KPro implant were broadly divided into three categories: autoimmune (n=12), chemical burns (n=11), and others (non‐autoimmune) (n=55). Three types of back plates were studied: 1) threaded (screw‐on) PMMA (n=39), 2) non‐threaded (snap‐on) PMMA (n=16) and 3) non‐threaded titanium back plates (n=23). Main outcome measured was incidence of RPM formation at 6 months after surgery that warranted removal by either YAG laser membranotomy or surgery.

Results The percentage of patients who developed RPM was greatest in the threaded PMMA group (46%), followed by the non‐threaded PMMA (31%), although this difference did not achieve statistical significance (p=0.5). The non‐threaded titanium group showed the least RPM formation (13%), which was significantly less than both the threaded PMMA (p=0.002) and the threadless PMMA (p=0.043) groups.

Conclusion Titanium KPro back plates induce less RPM than PMMA back plates, threaded or non‐threaded. It seems that the titanium plates in this setting are more tissue friendly and cause less inflammation than PMMA.
Activity of corneal nociceptive nerve fibers during allergic challenge of the ocular surface
Authors: GALLAR J , ACOSTA MC , LUNA C , BELMONTE C
Published: September 2009

Purpose The aim of this work was to study in vitro the spontaneous and stimulus‐evoked electrical activity of corneal nociceptive nerve fibers during acute allergic inflammation of the ocular surface induced in the guinea‐pig.

Methods Animals received i.p. 10% ovalbumin (OVA). 14 days later, a 10µl drop of OVA was applied topically to each eye. Blinking and scratching movements directed to the eye were measured during 10 min, and ocular symptoms (edema and hyperemia) and tear rate were measured. Animals were killed afterwards and both eyes were immediately excised and mounted in a superfused (32°C) recording chamber. Electrical activity of corneal sensory receptors was recorded from nerve filaments dissected from the ciliary nerves. Mechanical (calibrated von Frey hairs), thermal (bath solution temperature down to 20°C or up to 52°C), and chemical stimulation (30s‐pulses of 98%CO2) were performed. Spontaneous (SA) and stimulus‐evoked activity were analyzed.

Results After the allergic challenge, eye‐scratching behavior was present in 4 out of 15 animals and blinking movements increased from 1±0.05 to 26±5. Tearing also increased compared to control (33±3 vs. 5±1 mm). Compared to naive eyes, proportion of nociceptors with SA (17% vs. 5%) and spontaneous discharge rate (0.13±0.07 vs. 0.01±0.01 imp/s) were increased. Mechanical threshold of mechano‐nociceptive units decreased significantly (0.37±0.05 vs. 0.89±0.13 mN). Chemosensitivity of polymodal nociceptors was slightly increased (1.87±0.42 vs. 1.34±0.23 imp/s).

Conclusion Changes in corneal sensory nerve activity observed acutely after allergic challenge of the eye surface may constitute the basis of itching and discomfort sensations, and hypersensitivity observed in allergic patients.
Vasopressin receptors in ocular tissues and their impact on ocular hydrodynamics
Authors: BOGNER B , TOCKNER B , RUNGE CW , STROHMAIER C , GRABNER G , REITSAMER HA
Published: September 2009

Purpose To investigate the effect of intravenous applied vasopressin on aqueous flow and to localize involved receptor types in ocular tissues.

Methods In anesthetized rabbits mean arterial pressure (MAP), intraocular pressure (IOP) and orbital venous pressure (OVP) were measured by direct cannulation of the central ear artery, the vitreous, and the orbital venous sinus, respectively. Laser Doppler flowmetry was used to record CilBF continuously. Aqueous flow (AF) was measured simultaneously by fluorophotometry. After baseline measurements arginine‐vasopressin (AVP) was applied intravenously (infusion rate: 0.08 ng/kg/min). Immunostaining (SABC‐method, immunofluorescence) was performed to localize potential vasopressin receptors in ocular tissues.

Results AVP caused a considerable increase of MAP (+6,90±1,21%; p < 0,001), a significant decrease of IOP (‐9,56±2,35%; p = 0,003), a highly significant reduction of AF (‐21.34±4.08%; p < 0,001) and no significant change of CilBF (‐2.37±3.38%; n.s.). Immunofluorescent stainings show a characteristic pattern of V1‐ and V2‐receptor distribution. Both, V1 and V2 receptors are detectable in choroidal, ciliary and iridal vessels. Moreover, they are localized in the ciliary epithelium, whereas the labeling is more intensive in the non‐pigmented epithelium than in the pigmented epithelium.

Conclusion Although the applied dose of AVP did not changed CilBF considerably, a highly significant reduction of AF was observed. This suggests that the reduction of AF is predominantly caused by affecting the secretory mechanisms in the ciliary epithelium. The localization of vasopressin receptors in ciliary epithelium supports this assumption.
Chromosomal number aberrations and transformation in adult mouse retinal stem cells in vitro
Authors: DJOJOSUBROTO M , BOLLOTTE F , WIRAPATI P , RADTKE F , STAMENKOVIC I , ARSENIJEVIC Y
Published: September 2009

Purpose The therapeutic potential of stem cells on degenerative diseases and damaged tissues such as retinal degeneration has been recognized. Generation of high numbers of retinal stem cells (RSCs) in vitro would thus be beneficial for retinal transplantation. As long‐term cultivated cells might be unstable and have a risk of transformation, it is important to assess the stability of these cells.

Methods We analyzed chromosomal aberrations of RSC lines isolated from adult and postnatal day 1 mouse retinas. Then, selected cell lines were tested for anchorage‐dependent proliferation, and for possibility of transformation by transplantation in immunocompromised mice.

Results Aneuploidy occurred in all adult cell lines, albeit to different levels. Neonatal RSCs were the most stable and displaying a normal karyotype until at least passage 9. We observed that two of the adult RCS lines tested were transformed and identified several cell cycle proteins that might support the cell continuous proliferation and transformation.

Conclusion The aneuploidy level of adult RSCs did not necessarily correlate with cell transformation. Only the adult RSC lines passaged for longer period and with higher dilution ratio underwent transformation, showing that culture condition plays an important role in supporting the selection and growth of transformed cells.
Hypertonicity‐induced decrease in aquaporin‐4 expression in retinal pigmented epithelial cells
Authors: WILLERMAIN F , PIENS I , JANSSENS S , ARSENIJEVIC T , OP DE BEEK A , MAKHOUL M , BOLAKY N , CASPERS L , PERRET J , DELPORTE C
Published: September 2009

Purpose Osmotic gradients regulate subretinal water content and might be acutely changed during macular oedema. Moreover, since RPE cells express tight junctions, water molecules must use specific channels to cross their hydrophobic membrane. Aquaporins (AQP) are good candidates to assume this function. In this work, we investigated the effects of osmotic stress on the expression of AQP in RPE cells.

Methods ARPE‐19 cells were grown in different hypertonic conditions. AQP1 and AQP4 expressions were assessed by Western blot and RT‐PCR. Chemical inhibitors were used to specifically block lysosomes and proteasome function. Cell proliferation was investigated by BRDU incorporation, and cell viability by flow cytometry. Cell cycle was studied by Western blot and flow cytometry.

Results Hypertonic stress rapidly decreased AQP4 expression on ARPE cells. The effect was reversed by proteasome inhibition, but was likely ubiquitinylation‐independent. At 24h post‐hypertonic stress, cell viability was not affected but cell proliferation was decreased. Cell cycle was also modified as the percentage of cells in G0/G1 phase decreased and the percentage of cells in S and G2/M phase increased.

Conclusion Hypertonic stress strongly reduced AQP4 expression and RPE cell proliferation. Those results might contribute to our understanding of macular oedema formation.
The Bmi1 polycomb gene as a target for therapies against retinal degeneration
Authors: ARSENIJEVIC Y , VAN LOHUIZEN M , ZENCAK D
Published: September 2009

Purpose In several neurodegenerative diseases the reactivation of cell cycle proteins is a key event that precedes neuronal apoptosis. We asked whether a similar phenomenon occurs in Rd1 mice, a model of retinitis pigmentosa widely used to study photoreceptor (PR) loss.

Methods We used different knockout mouse models to reveal whether proteins involved in the cell cycle regulation are responsible for photoreceptor loss in the Rd1 mouse.

Results At P12, an early stage of the disease, Rd1 mice displayed an increased expression of CDK4 and CDK2 among PR nuclei. PRs also undergo DNA synthesis. At P12, the polycomb protein Bmi1 was expressed in virtually all the nuclei in the inner and outer nuclear layer of both wild‐type (WT) and Rd1 mice. Bmi1 promotes cell cycle progression via the repression of tumor suppressor genes. We reasoned that Bmi1 deletion could impede the aberrant CDK reactivation that characterizes neuronal apoptosis and may therefore delay retinal degeneration. We compared the histology of WT, Rd1 and Rd1;Bmi1‐/‐ and observed the presence of 7 rows of PRs in Rd1;Bmi1‐/‐ mice at P33, while Rd1 littermates displayed a single scattered row of PRs. ERG recordings revealed the ability of Rd1:Bmi1‐/‐ retinas to respond to light stimuli. Both DNA synthesis and CDK4 were strongly decreased in Rd1;Bmi1‐/‐ mice, respectively by 70% and 50% as compared to Rd1 littermates.

Conclusion In conclusion, our data show for the first time a mechanism of retina degeneration involving a reactivation of the cell cycle that precedes PR death in Rd1 mice and reveal that the partial inhibition of cell cycle re‐entry strongly delays PR loss.