Effective accumulation of polyion complex micelle to experimental choroidal neovascularization in rats

AbstractExudative age-related macular degeneration, characterized by choroidal neovascularization (CNV), is a major cause of visual loss. In this study, we examined the distribution of the polyion complex (PIC) micelle encapsulating FITC-P(Lys) in blood and in experimental CNV in rats to investigate whether PIC micelle can be used for treatment of CNV. We demonstrate that PIC micelle has long-circulating characteristics, accumulating to the CNV lesions and is retained in the lesion for as long as 168 h after intravenous administration. These results raise the possibility that PIC micelles can be used for achieving effective drug targeting to CNV

Allelic association results for D2S0276i and nine SNPs in the <i>COL4A4</i> and <i>RHBDD1</i> gene regions.

<p>1, major allele; 2, minor allele; OR, odds ratio; SNP, single nucleotide polymorphism.</p><p>Position is distance from short arm telomere. P values were calculated by χ² test 2×2 contingency table. We corrected <i>P</i> values (<i>P</i>c) of D2S0276i and 5 SNPs in the combined stage for multiple testing by Bonferroni's method and Haploview program using 10,000 permutations, respectively.</p

Association analysis of single nucleotide polymorphisms (SNPs) across the <i>COL4A4</i> and <i>RHBDD1</i> gene regions in 574 patients and 608 controls.

<p>The upper panels depict distribution of association results of D2S0276i and SNPs in <i>COL4A4</i> and <i>RHBDD1</i>. The results of monomorphic SNPs are not shown. The lower panels show the linkage disequilibrium structure in the <i>COL4A4</i> and <i>RHBDD1</i> regions; brighter red indicates higher D’.</p

Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci.

Exfoliation syndrome (XFS) is the most common known risk factor for secondary glaucoma and a major cause of blindness worldwide. Variants in two genes, LOXL1 and CACNA1A, have previously been associated with XFS. To further elucidate the genetic basis of XFS, we collected a global sample of XFS cases to refine the association at LOXL1, which previously showed inconsistent results across populations, and to identify new variants associated with XFS. We identified a rare protective allele at LOXL1 (p.Phe407, odds ratio (OR) = 25, P = 2.9 × 10-14) through deep resequencing of XFS cases and controls from nine countries. A genome-wide association study (GWAS) of XFS cases and controls from 24 countries followed by replication in 18 countries identified seven genome-wide significant loci (P &lt; 5 × 10-8). We identified association signals at 13q12 (POMP), 11q23.3 (TMEM136), 6p21 (AGPAT1), 3p24 (RBMS3) and 5q23 (near SEMA6A). These findings provide biological insights into the pathology of XFS and highlight a potential role for naturally occurring rare LOXL1 variants in disease biology

A common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome

Exfoliation syndrome (XFS) is the most common recognizable cause of open-angle glaucoma worldwide. To better understand the etiology of XFS, we conducted a genome-wide association study (GWAS) of 1,484 cases and 1,188 controls from Japan and followed up the most significant findings in a further 6,901 cases and 20,727 controls from 17 countries across 6 continents. We discovered a genome-wide significant association between a new locus (CACNA1A rs4926244) and increased susceptibility to XFS (odds ratio (OR) = 1.16, P = 3.36 × 10(-11)). Although we also confirmed overwhelming association at the LOXL1 locus, the key SNP marker (LOXL1 rs4886776) demonstrated allelic reversal depending on the ancestry group (Japanese: OR(A allele) = 9.87, P = 2.13 × 10(-217); non-Japanese: OR(A allele) = 0.49, P = 2.35 × 10(-31)). Our findings represent the first genetic locus outside of LOXL1 surpassing genome-wide significance for XFS and provide insight into the biology and pathogenesis of the disease

A common variant mapping to <i>CACNA1A </i>is associated with susceptibility to exfoliation syndrome

Author manuscript available from PMC http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4605818/Exfoliation syndrome (XFS) is the most common recognizable cause of open-angle glaucoma worldwide. To better understand the etiology of XFS, we conducted a genome-wide association study (GWAS) of 1,484 cases and 1,188 controls from Japan and followed up the most significant findings in a further 6,901 cases and 20,727 controls from 17 countries across 6 continents. We discovered a genome-wide significant association between a new locus (CACNA1A rs4926244) and increased susceptibility to XFS (odds ratio (OR) = 1.16, P = 3.36 × 10−11). Although we also confirmed overwhelming association at the LOXL1 locus, the key SNP marker (LOXL1 rs4886776) demonstrated allelic reversal depending on the ancestry group (Japanese: ORA allele = 9.87, P = 2.13 × 10−217; non-Japanese: ORA allele = 0.49, P = 2.35 × 10−31). Our findings represent the first genetic locus outside of LOXL1 surpassing genome-wide significance for XFS and provide insight into the biology and pathogenesis of the disease

Genetic Association Study Of Exfoliation Syndrome Identifies A Protective Rare Variant At Loxl1 And Five New Susceptibility Loci

Exfoliation syndrome (XFS) is the most common known risk factor for secondary glaucoma and a major cause of blindness worldwide. Variants in two genes, LOXL1 and CACNA1A, have previously been associated with XFS. To further elucidate the genetic basis of XFS, we collected a global sample of XFS cases to refine the association at LOXL1, which previously showed inconsistent results across populations, and to identify new variants associated with XFS. We identified a rare protective allele at LOXL1 (p.Phe407, odds ratio (OR) = 25, P = 2.9 x 10(-14)) through deep resequencing of XFS cases and controls from nine countries. A genome-wide association study (GWAS) of XFS cases and controls from 24 countries followed by replication in 18 countries identified seven genome-wide significant loci (P < 5 x 10(-8)). We identified association signals at 13q12 (POMP), 11q23.3 (TMEM136), 6p21 (AGPAT1), 3p24 (RBMS3) and 5q23 (near SEMA6A). These findings provide biological insights into the pathology of XFS and highlight a potential role for naturally occurring rare LOXL1 variants in disease biology.Wo