Search

Primary open-angle glaucoma (POAG) is the most common form of glaucoma, prevalent in approximately 1-2% of Caucasians in the UK over the age of 40. It is characterised by an open anterior chamber angle, raised intraocular pressure (IOP) and optic nerve damage leading to loss of sight. The myocilin gene (MYOC) is the most common glaucoma-causing gene, accounting for ~2% of British POAG cases. 358 patients were selected for next generation sequencing (NGS) with the following selection criteria: Caucasian ethnicity, intraocular pressure (IOP) 21-40 mm Hg, cup:disc ratio ≥0.6 and visual field mean deviation ≤-3. The entire MYOC gene (17,321 bp) was captured including the promoter, introns, UTRs and coding exons. We identify 12 exonic variants (one stop-gain, five missense and six synonymous variants), two promoter variants, 133 intronic variants, two 3' UTR variants and 23 intergenic variants. Four known or predicted pathogenic exonic variants (p.R126W, p.K216K, p.Q368* and p.T419A) were identified across 11 patients, which accounts for 3.07% of this POAG cohort. This is the first time that the entire region of MYOC has been sequenced and variants reported for a cohort of POAG patients.

Humans undergo biological ageing at different rates. This associates with functional decline in a number of physiological systems and increasing incidence of age-related pathologies. The discovery of robust biomarkers of ageing could be used to identify early divergence from a path of healthy ageing towards age-related disease. In the present study, we undertook proteomic analysis of plasma from healthy young men (mean age = 21.4 ± 1.5 years) and healthy midlife men (mean age = 57.0 ± 1.6 years). We identified 12 spots including transferrin, complement C3b and transthyretin that differed in abundance between the age groups. Transferrin spots showed an acidic pI shift in older males. Sandwich ELISAs were used to investigate the changes further. C3b levels were below the level of detection by ELISA and plasma concentrations of total transferrin or transthyretin were not different between the age groups studied here. However, analysis of transferrin N-glycan structures showed an increase in terminal galactose residues in older men, suggesting that the loss of terminal N-acetyl neuraminic acid residues contributes to the more acid pI of transferrin spots observed with age. Terminal galactosylation of transferrin may be a biomarker of healthy ageing and is now under investigation in the MARK-AGE study., (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Apoptosis is a key event in the control of inflammation. However, for this to be successful, dying cells must efficiently and effectively communicate their presence to phagocytes to ensure timely removal of dying cells. Here, we consider apoptotic cell-derived extracellular vesicles and the role of contained lipids and lipid mediators in ensuring effective control of inflammation. We discuss key outstanding issues in the study of cell death and cell communication, and introduce the concept of the 'active extracellular vesicle' as a metabolically active and potentially changing intercellular communicator. [ABSTRACT FROM AUTHOR]