“
“Neovascular age-related macular degeneration (AMD) is www.selleckchem.com/products/ABT-263.html the leading cause of legal blindness in patients over the age of 50 in the western world. Intravitreally administered anti-VEGF drugs have been developed to halt neovascular growth in AMD. Randomized trials have demonstrated the excellent safety profile

and significant benefit of anti-VEGF therapy in maintaining vision. Aflibercept (Eylea(R); Regeneron, NY, USA) is a soluble decoy receptor against VEGF that offers greater potency and binding affinity than other anti-VEGF drugs. Having received US FDA approval for neovascular AMD in November 2011, aflibercept given every 8 weeks after a loading dose was ‘clinically equivalent’ and statistically noninferior to the current FDA-approved therapy ranibizumab (Lucentis(R); Genentech, CA, USA), given every 4 weeks. This article discusses the clinical background selleck chemicals llc of AMD, development of aflibercept, results of the clinical trials and the future role of aflibercept in ocular neovascular diseases.”
“Haploinsufficiency of Euchromatin histone methyltransferase 1 (EHMT1), a chromatin modifying enzyme, is the cause of Kleefstra syndrome (KS). KS is an intellectual disability (ID) syndrome, with general developmental delay, hypotonia, and craniofacial dysmorphisms as additional core

features. Recent studies have been focused on the role of EHMT1 in learning and memory, linked to the ID phenotype of KS patients. In this study we used the Ehmt1(+/-) mouse model, and investigated whether the core features of KS were mimicked in these mice. When comparing Ehmt1(+/-) mice to wildtype littermates we observed delayed postnatal growth, eye opening, LY2606368 price ear opening, and upper incisor eruption, indicating a delayed postnatal development

Furthermore, tests for muscular strength and motor coordination showed features of hypotonia in young Ehmt1(+/-) mice. Lastly, we found that Ehmt1(+/-) mice showed brachycephalic crania, a shorter or bent nose, and hypertelorism, reminiscent of the craniofacial dysmorphisms seen in KS. In addition, gene expression analysis revealed a significant upregulation of the mRNA levels of Runx2 and several other bone tissue related genes in P28 Ehmt1(+/-) mice. Runx2 immunostaining also appeared to be increased. The mRNA upregulation was associated with decreased histone H3 lysine 9 dimethylation (H3K9me2) levels, the epigenetic mark deposited by Ehmt1, in the promoter region of these genes. Together, Ehmt1(+/-) mice indeed recapitulate KS core features and can be used as an animal model for Kleefstra syndrome. The increased expression of bone developmental genes in the Ehmt1(+/-) mice likely contributes to their cranial dysmorphisms and might be explained by diminished Ehmt1-induced H3K9 dimethylation. (C) 2013 Elsevier Inc. All rights reserved.