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Background Rare Eye Diseases (RED) are the leading cause of visual impairment and blindness for children and young adults in Europe. This heterogeneous group of conditions includes over 900 disorders ranging from relatively prevalent disorders such as retinitis pigmentosa to very rare entities such as developmental eye anomalies. A significant number of patients with RED have an underlying genetic etiology. One of the aims of the European Reference Network for Rare Eye Diseases (ERN–EYE) is to facilitate improvement in diagnosis of RED in European member states. Main body Technological advances have allowed genetic and genomic testing for RED. The outcome of genetic testing allows better understanding of the condition and allows reproductive and therapeutic options. The increase of the number of clinical trials for RED has provided urgency for genetic testing in RED. A survey of countries participating in ERN-EYE demonstrated that the majority are able to access some forms of genomic testing. However, there is significant variability, particularly regarding testing as part of clinical service. Some countries have a well-delineated rare disease pathway and have a national plan for rare diseases combined or not with a national plan for genomics in medicine. In other countries, there is a well-established organization of genetic centres that offer reimbursed genomic testing of RED and other rare diseases. Clinicians often rely upon research-funded laboratories or private companies. Notably, some member states rely on cross-border testing by way of an academic research project. Consequently, many clinicians are either unable to access testing or are confronted with long turnaround times. Overall, while the cost of sequencing has dropped, the cumulative cost of a genomic testing service for populations remains considerable. Importantly, the majority of countries reported healthcare budgets that limit testing. Short conclusion Despite technological advances, critical gaps in genomic testing remain in Europe, especially in smaller countries where no formal genomic testing pathways exist. Even within larger countries, the existing arrangements are insufficient to meet the demand and to ensure access. ERN-EYE promotes access to genetic testing in RED and emphasizes the clinical need and relevance of genetic testing in RED.

© 2015 Macmillan Publishers Limited. All rights reserved. A central question in protein evolution is the extent to which naturally occurring proteins sample the space of folded structures accessible to the polypeptide chain. Repeat proteins composed of multiple tandem copies of a modular structure unit are widespread in nature and have critical roles in molecular recognition, signalling, and other essential biological processes. Naturally occurring repeat proteins have been re-engineered for molecular recognition and modular scaffolding applications. Here we use computational protein design to investigate the space of folded structures that can be generated by tandem repeating a simple helix-loop-helix-loop structural motif. Eighty-three designs with sequences unrelated to known repeat proteins were experimentally characterized. Of these, 53 are monomeric and stable at 95°C, and 43 have solution X-ray scattering spectra consistent with the design models. Crystal structures of 15 designs spanning a broad range of curvatures are in close agreement with the design models with root mean square deviations ranging from 0.7 to 2.5Å. Our results show that existing repeat proteins occupy only a small fraction of the possible repeat protein sequence and structure space and that it is possible to design novel repeat proteins with precisely specified geometries, opening up a wide array of new possibilities for biomolecular engineering.

The aim of this study was to verify the acute effects of alpha-adrenoreceptor agonist eyedrop administration on visual field parameters and ocular perfusion pressure (OPP) in patients affected by primary open-angle glaucoma.A prospective, randomized double-blind study was carried out. Sixty-four glaucomatous subjects were enrolled in the clinical trial and subsequently separated into four study groups, of 16 patients each, to compare the systemic and ocular effects of placebo, clonidine 0.125%, apraclonidine 1.0% and brimonidine 0.2%.No significant variations in the ocular or systemic parameters were observed after placebo administration. All the alpha-adrenoreceptor agonist compounds induced a significant reduction of the intraocular pressure. Clonidine induced significant modifications of mean blood pressure, OPP and visual field indices. The acute administration of apraclonidine did not affect both mean blood pressure and OPP, but a worsening of the visual field was nevertheless recorded. The analyzed parameters did not significantly vary after brimonidine instillation.The present findings demonstrate that the lack of effects on the blood flow and the absence of vasomotor activity at the level of the posterior pole exhibited by brimonidine is related to its alpha-2 selectivity, as appears by comparing this compound with the other alpha-agonists available for the management of glaucoma.

PURPOSE. To investigate the cause of recurrent central retinal vein occlusion in a 26-year-old white woman. METHODS. Case report. Complete blood analyses were done, including HLA tissue typing, immunoserologic and coagulation tests, with cardiovascular and capillaroscopy investigations. Factor V:R506Q and prothrombin 20210 G/A mutations were checked by polymerase chain reaction and restriction enzyme analysis. RESULTS. DNA analysis showed the patient to be heterozygous for factor V:R506Q mutation. During a follow-up of 18-months, after starting anticoagulant therapy, the patient had not suffered from any other ocular or systemic occlusive vascular accident. CONCLUSIONS. The R506Q factor V gene mutation may be associated with recurrent central retinal vein occlusions. Genetic investigation should be promptly recommended in thrombotic patients to establish a specific preventive treatment.

A multidisciplinary approach based on molecular dynamics (MD) simulations using homology models NMR spectroscopy and a variety of biophysical techniques was used to efficiently improve the thermodynamic stability of armadillo repeat proteins (ArmRPs). ArmRPs can form the basis of modular peptide recognition and the ArmRP version on which synthetic libraries are based must be as stable as possible. The 42 residue internal Arm repeats had been designed previously using a sequence consensus method. Heteronuclear NMR revealed unfavorable interactions present at neutral but absent at high pH. Two lysines per repeat were involved in repulsive interactions and stability was increased by mutating both to glutamine. Five point mutations in the capping repeats were suggested by the analysis of positional fluctuations and configurational entropy along multiple MD simulations. The most stabilizing single C cap mutation Q240L was inferred from explicit solvent MD simulations in which water penetrated the ArmRP. All mutants were characterized by temperature and denaturant unfolding studies and the improved mutants were established as monomeric species with cooperative folding and increased stability against heat and denaturant. Importantly the mutations tested resulted in a cumulative decrease of flexibility of the folded state in silico and a cumulative increase of thermodynamic stability in vitro. The final construct has a melting temperature of about 85 degrees C 14.5 degrees higher than the starting sequence. This work indicates that in silico studies in combination with heteronuclear NMR and other biophysical tools may provide a basis for successfully selecting mutations that rapidly improve biophysical properties of the target proteins.

Traditional treatment for uveal melanoma is the enucleation of the eye with outcomes cosmetically unacceptable and loss of useful vision. Plaque brachytherapy, compared to enucleation, had the advantage to preserve the eye with outcomes cosmetically acceptable and preservation of vision.From July 1990 to December 2009 one hundred forty-two (142) patients (51 males and 91 females) with small to medium uveal melanoma were treated with 106Ru plaque brachytherapy. The patients underwent a complete staging before brachytherapy with indirect ophthalmoscopy and ultrasounds. Mean tumour thickness was 3.26 mm (1.6-6 mm). The dose scheduled was 80-100 Gy to the apex with a maximum dose of 800 Gy to the sclera.One hundred forty-two have been treated, nine patients had lost the follow-up and drop out; 133 patients were assessed. Mean follow-up was 7.7 years (6 months-18 years). The overall survival at 5, 10 and 15 years was 92%, 85% and 78% respectively. Cancer fee survival was 95%, 90% and 83%, respectively at 5, 10 and 15 year. Radiation-induced toxicity was represented in 47 patients with a 5 year actuarial survival rate free from complications of 54%.106Ru plaque brachytherapy is a valid approach for treatment of uveal melanoma. This technique is efficacy and safe, with a low toxicity profile.