Macular Retinal Ganglion Cell Complex Thickness and Its Relationship to the Optic Nerve Head Topography in Glaucomatous Eyes with Hemifield Defects

Purpose. To evaluate the relationship between the macular ganglion cell complex (mGCC) thickness, which is the sum of the retinal nerve fiber, ganglion cell, and inner plexiform layers, measured with a spectral-domain optical coherence tomograph and the optic nerve head topography measured with a confocal scanning laser ophthalmoscope in glaucomatous eyes with visual field defects localized predominantly to either hemifield. Materials and Methods. The correlation between the mGCC thickness in hemispheres corresponding to hemifields with and without defects (damaged and intact hemispheres, respectively) and the optic nerve head topography corresponding to the respective hemispheres was evaluated in 18 glaucomatous eyes. Results. The mGCC thickness was significantly correlated with the rim volume, mean retinal nerve fiber layer thickness, and cross-sectional area of the retinal nerve fiber layer in both the intact and the damaged hemispheres (P < .05). Discussion. For detecting very early glaucomatous damage of the optic nerve, changes in the thicknesses of the inner retina in the macular area and peripapillary RNFL as well as rim volume changes in the optic nerve head are target parameters that should be carefully monitored

Identification of RNF213 as a Susceptibility Gene for Moyamoya Disease and Its Possible Role in Vascular Development

もやもや病感受性遺伝子の特定とその機能についての発見. 京都大学プレスリリース. 2011-7-21.Background Moyamoya disease is an idiopathic vascular disorder of intracranial arteries. Its susceptibility locus has been mapped to 17q25.3 in Japanese families, but the susceptibility gene is unknown. Methodology/Principal Findings Genome-wide linkage analysis in eight three-generation families with moyamoya disease revealed linkage to 17q25.3 (P<10-4). Fine mapping demonstrated a 1.5-Mb disease locus bounded by D17S1806 and rs2280147. We conducted exome analysis of the eight index cases in these families, with results filtered through Ng criteria. There was a variant of p.N321S in PCMTD1 and p.R4810K in RNF213 in the 1.5-Mb locus of the eight index cases. The p.N321S variant in PCMTD1 could not be confirmed by the Sanger method. Sequencing RNF213 in 42 index cases confirmed p.R4810K and revealed it to be the only unregistered variant. Genotyping 39 SNPs around RNF213 revealed a founder haplotype transmitted in 42 families. Sequencing the 260-kb region covering the founder haplotype in one index case did not show any coding variants except p.R4810K. A case-control study demonstrated strong association of p.R4810K with moyamoya disease in East Asian populations (251 cases and 707 controls) with an odds ratio of 111.8 (P = 10−119). Sequencing of RNF213 in East Asian cases revealed additional novel variants: p.D4863N, p.E4950D, p.A5021V, p.D5160E, and p.E5176G. Among Caucasian cases, variants p.N3962D, p.D4013N, p.R4062Q and p.P4608S were identified. RNF213 encodes a 591-kDa cytosolic protein that possesses two functional domains: a Walker motif and a RING finger domain. These exhibit ATPase and ubiquitin ligase activities. Although the mutant alleles (p.R4810K or p.D4013N in the RING domain) did not affect transcription levels or ubiquitination activity, knockdown of RNF213 in zebrafish caused irregular wall formation in trunk arteries and abnormal sprouting vessels. Conclusions/Significance We provide evidence suggesting, for the first time, the involvement of RNF213 in genetic susceptibility to moyamoya disease