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The article presents a study which looks at the impact of annexins A5 and A6 deficiency on the skeletal development of mice. To examine skeletal elements, the researchers used histologic, ultrastructural and peripheral quantitative computed tomographic methods which revealed that mineralization and skeletal development were not significantly affected in mutant mice. They performed the experiments in accordance with the animal ethics guidelines of the Murdoch Children's Research Institute and the German animal protection law.

Age-related macular degeneration is the most common form of legal blindness in westernized societies, and polymorphisms in the gene encoding complement factor H (CFH) are associated with susceptibility to age-related macular degeneration in more than half of affected individuals. To investigate the relationship between complement factor H (CFH) and retinal disease, we performed functional and anatomical analysis in 2-year-old CFH-deficient (cfh-/-) mice. cfh-/- animals exhibited significantly reduced visual acuity and rod response amplitudes on electroretinography compared with age-matched controls. Retinal imaging by confocal scanning laser ophthalmoscopy revealed an increase in autofluorescent subretinal deposits in the cfh-/- mice, whereas the fundus and vasculature appeared normal. Examination of tissue sections showed an accumulation of complement C3 in the neural retina of the cfh-/- mice, together with a decrease in electron-dense material, thinning of Bruch's membrane, changes in the cellular distribution of retinal pigment epithelial cell organelles, and disorganization of rod photoreceptor outer segments. Collectively, these data show that, in the absence of any specific exogenous challenge to the innate immune system, CFH is critically required for the long-term functional health of the retina. [ABSTRACT FROM AUTHOR]

The development of the devastating neurodegenerative condition, Alzheimer's disease, is strongly associated with amyloid-β3 (Aβ) deposition, neuronal apoptosis, and cell loss. Here, we provide evidence that implicates these same mechanisms in the retinal disease glaucoma, a major cause of irreversible blindness world- wide, previously associated simply with the effects of intraocular pressure. We show that Aβ colocalizes with apoptotic retinal ganglion cells (RGC) in experimental glaucoma and induces significant RGC apoptosis in vivo in a dose- and time-dependent manner. We demonstrate that targeting different components of the Aβ formation and aggregation pathway can effectively reduce glaucomatous RGC apoptosis in vivo, and finally, that combining treatments (triple therapy) is more effective than monotherapy. Our work suggests that targeting the Aβ pathway provides a therapeutic avenue in glaucoma management. Furthermore, our work demonstrates that the combination of agents affecting multiple stages in the Aβ pathway may be the most effective strategy in Aβ-related diseases. [ABSTRACT FROM AUTHOR]

Eukaryotic cells contain various Ca2+-effector proteins that mediate cellular responses to changes in intracellular Ca2+ levels. A unique class of these proteins-annexins-can bind to certain membrane phospholipids in a Ca2+-dependent manner, providing a link between Ca2+ signalling and membrane functions. By forming networks on the membrane surface, annexins can function as organizers of membrane domains and membrane-recruitment platforms for proteins with which they interact. These and related properties enable annexins to participate in several otherwise unrelated events that range from membrane dynamics to cell differentiation and migration. [ABSTRACT FROM AUTHOR]

Apoptotic nerve cell death is implicated in the pathogenesis of several devastating neurodegenerative conditions, including glaucoma and Alzheimer's and Parkinson's diseases. We have devised a noninvasive real-time imaging technique using confocal laser-scanning ophthalmoscopy to visualize single nerve cell apoptosis in vivo, which allows longitudinal study of disease processes that has not previously been possible. Our method utilizes the unique optical properties of the eye, which allow direct microscopic observation of nerve cells in the retina. We have been able to image changes occurring in nerve cell apoptosis over hours, days, and months and show that effects depend on the magnitude of the initial apoptotic inducer in several models of neurodegenerative disease in rat and primate. This technology enables the direct observation of single nerve cell apoptosis in experimental neurodegeneration, providing the opportunity for detailed investigation of fundamental disease mechanisms and the evaluation of interventions with potential clinical applications, together with the possibility of taking this method through to patients. [ABSTRACT FROM AUTHOR]

Examines the physiological functions of annexins. Role in the regulation of calcium channel activity and vesicle trafficking; Resistance of annexins to apoptosis; Importance in the detection of apoptotic cells.

Studies the role of conserved nuclear elements in mammalian gene regulation. Association between enhancer or promoter activities and repetitive elements; Effect of phorbol ester and ionophore on endogenous gene expression; Interaction between annexin VI LINE-2 fragments and the basal transcription complex.

A plasmid cDNA library prepared from a T-lymphocyte clone of murine strain B10.A origin was screened by cross-species DNA hybridisation using a partial human p68 cDNA clone, identified as containing coding sequences for previously determined amino-acid sequences. The longest p68 cDNA insert from this library and a full-length cDNA insert from a second similar library were fully sequenced. A comparison of the derived amino-acid sequence with that of human p68 revealed extensive homology (95% overall). Homology at the nucleotide level was 89% in the open reading frame and 85% and 50% in the 5' (33 nucleotides) and 3' (347 nucleotides) non-coding regions respectively. Eight segments of internal homology were observed, each containing a highly conserved consensus region of 17 amino acids correlating with that described for several membrane associated calcium-binding proteins [Geisow, M. J., Fritsche, U., Hexham, J. M. & Johnson, T. (1986) Nature (Lond.) 320, 636-638]. These results provide further evidence that p68 is a member of the same gene family as p32, p36 and lipocortin I and demonstrate an unusually high level of inter-species sequence conservation of p68 between mouse and human. [ABSTRACT FROM AUTHOR]

Leucine-rich a-2-glycoprotein 1 (LRG1) is a candidate therapeutic target for treating the neovascular form of age-related macular degeneration (nvAMD). In this study we examined the expression of LRG1 in eyes of nvAMD patients. Choroidal neovascular membranes (CNVMs) from patients who underwent submacular surgery for retinal pigment epithelium–choroid graft transplantation were collected from 5 nvAMD patients without any prior intravitreal anti-VEGF injection, and from six patients who received intravitreal anti-VEGF injections before surgery. As controls free of nvAMD, retina sections were obtained from the eyes resected from a patient with lacrimal sac tumor and from a patient with neuroblastoma. CNVMs were immunostained for CD34, LRG1, and α-smooth muscle actin (α-SMA). Aqueous humor samples were collected from 58 untreated-naïve nvAMD patients prior to the intravitreal injection of anti-VEGF and 51 age-matched cataract control patients, and LRG1 concentration was measured by ELISA. The level of LRG1 immunostaining is frequently high in both the endothelial cells of the blood vessels, and myofibroblasts in the surrounding tissue of CNVMs of treatment-naïve nvAMD patients. Furthermore, the average concentration of LRG1 was significantly higher in the aqueous humor of nvAMD patients than in controls. These observations provide a strong experimental basis and scientific rationale for the progression of a therapeutic anti-LRG1 monoclonal antibody into clinical trials with patients with nvAMD. [ABSTRACT FROM AUTHOR]