We executed a genome-wide association scan for age-related macular degeneration (AMD) in 2,157 cases and 1,150 controls. Our results validate AMD susceptibility loci near CFH (P < 10 −75), ARMS2 (P < 10 −59), C2/CFB (P < 10 −20), C3 (P < 10 −9 ), and CFI (P < 10
−6). We compared our top findings with the Tufts/Massachusetts General Hospital genome-wide association study of advanced AMD (821 cases, 1,709 controls) and genotyped 30 promising markers in additional individuals (up to 7,749 cases and 4,625 controls). With these data, we identified a susceptibility locus near TIMP3 (overall P = 1.1 × 10), a metalloproteinase involved in degradation of the extracellular matrix and previously implicated in early-onset maculopathy. In addition, our data revealed strong association signals with alleles at two loci (LIPC, P = 1.3 × 10 −7; CETP, P = 7.4 × 10 −7 ) that were previously associated with high-density lipoprotein cholesterol (HDL-c) levels in blood. Consistent with the hypothesis that HDL metabolism is associated with AMD pathogenesis, we also observed association with AMD of HDL-c-associated alleles near LPL (P = 3.0 × 10 −3) and ABCA1 (P = 5.6 × 10
−4). Multilocus analysis including all susceptibility loci showed that 329 of 331 individuals (99%) with the highest-risk genotypes were cases, and 85% of these had advanced AMD. Our studies extend the catalog of AMD associated loci, help identify individuals at high risk of disease, and provide clues about underlying cellular pathways that should eventually lead to new therapies.genome-wide association study | single nucleotide polymorphism A ge-related macular degeneration (AMD) is a progressive neurodegenerative disease and a common cause of blindness in the elderly population, particularly in developed countries (1). The disease affects primarily the macular region of the retina, which is necessary for sharp central vision. An early hallmark of AMD is the appearance of drusen, which are extracellular deposits of proteins and lipids under the retinal pigment epithelium (RPE). As the disease progresses, drusen grow in size and number. In advanced stages of AMD, atrophy of the RPE (geographic atrophy) and/or development of new blood vessels (neovascularization) result in death of photoreceptors and central vision loss.
3D printing is a method of manufacturing in which materials, such as plastic or metal, are deposited onto one another in layers to produce a three dimensional object, such as a pair of eye glasses or other 3D objects. This process contrasts with traditional ink-based printers which produce a two dimensional object (ink on paper). To date, 3D printing has primarily been used in engineering to create engineering prototypes. However, recent advances in printing materials have now enabled 3D printers to make objects that are comparable with traditionally manufactured items. In contrast with conventional printers, 3D printing has the potential to enable mass customisation of goods on a large scale and has relevance in medicine including ophthalmology. 3D printing has already been proved viable in several medical applications including the manufacture of eyeglasses, custom prosthetic devices and dental implants. In this review, we discuss the potential for 3D printing to revolutionise manufacturing in the same way as the printing press revolutionised conventional printing. The applications and limitations of 3D printing are discussed; the production process is demonstrated by producing a set of eyeglass frames from 3D blueprints.
Age-related macular degeneration (AMD), the leading cause of blindness in the elderly, is a complex disease to study because of the potential role of demographic, environmental, and other systemic risk factors, such as age, sex, race, light exposure, diet, smoking, and underlying cardiovascular disease which may contribute to the pathogenesis of this disease. Recently, single nucleotide polymorphisms, DNA sequence variations found within the complement Factor H gene, have been found to be strongly associated with the development of AMD in Caucasians. One single nucleotide polymorphism, Tyr402His, was associated with approximately 50% of AMD cases. We review recent developments in the molecular biology of AMD, including single nucleotide polymorphisms within the Factor H gene, which may predispose individuals to the susceptibility of AMD as well as single nucleotide polymorphisms that may confer a protective effect. Taken together these findings help to provide new insights into the central issues surrounding the pathogenesis of AMD.
The human gene (RB) that determines susceptibility to hereditary retinoblastoma has been identified recently by molecular genetic techniques. Previous results indicate that complete inactivation of the RB gene is required for tumour formation. As a 'cancer suppressor' gene, RB thus functions in a manner opposite to that of most other oncogenes. Sequence analysis of RB complementary DNA clones demonstrated a long open reading frame encoding a hypothetical protein with features suggestive of a DNA-binding function. To further substantiate and identify the RB protein, we have prepared rabbit antisera against a trypE-RB fusion protein. The purified anti-RB IgG immunoprecipitates a protein doublet with apparent relative molecular mass (Mr) of 110,000-114,000. The specific protein(s) are present in all cell lines expressing normal RB mRNA, but are not detected in five retinoblastoma cell lines examined. The RB protein can be metabolically labelled with 32P-phosphoric acid, indicating that it is a phosphoprotein. Biochemical fractionation and immunofluorescence studies demonstrate that the majority of the protein is located within the nucleus. Furthermore, the protein can be retained by and eluted from DNA-cellulose columns, suggesting that it is associated with DNA binding activity. Taken together, these results imply that the RB gene product may function in regulating other genes within the cell.
The complete amino acid sequence of bovine S antigen (48-kDa protein) has been determined by cDNA and partial amino acid sequencing. A 1623-base-pair (bp) cDNA contains an open reading frame coding for a protein of 404 amino acids (45,275 Da). Tryptic peptides and cyanogen bromide peptides of native bovine S antigen were purified and partially sequenced. All of these peptides were accounted for in the long open reading frame. Searching of the National Biomedical Research Foundation data bank revealed no extensive sequence homology between S antigen and other proteins. However, there are local regions of sequence similarity with a transducin, including the sites subject to ADP-ribosylation by Bordetella pertussis and cholera toxins and the phosphoryl binding-sites. Secondary structure prediction and circular dichroic spectroscopy show that S antigen is composed predominantly of a-sheet conformation. Acid-catalyzed methanolysis suggests the presence of low levels of carbohydrate in the molecule.
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