A Neurophysiological Study on the Sympathetic Premotor Nuclei in the Pons and Medulla Oblongata

The aim of this study was to neurophysiologically demonstrate the activities of the premotor nuclei of sympathetic  vasomotion, by capturing the diachronic changes in the action potentials which are generated in  the pons and medulla oblongata. To do so, ten male Wistar rats weighing 300g were used as subjects.  Microelectrodes were inserted in the muscular branch of the sciatic nerve and the ventral side of the pons  and medulla oblongata, and the muscle sympathetic nerve activity (MSA) was induced. The regular spontaneous  action potentials, which synchronize with muscle sympathetic nerve activity, were observed in the  rostral ventrolateral medulla oblongata (RVLM), and the differences among the action potentials of individual  cells of the RVLM region noted. Autonomic postganglionic nerves are controlled in turn by preganglionic  nerves that originate from specific nuclei in the medulla. These nerves directly influence cardiovascular  function by regulating the rate and force of contraction of the heart and the diameter of blood  vessels. RVLM cells in fact exert a widespread control over the sympathetic outflow. We conclude from the  experiment that premotor nuclei of sympathetic vasomotion exist in the RVLM.

An experimental study on the peripheral autonomic nerve potential in the spinal cord injury model by microneurography

The purpose of the present investigation was to analyze the effects of spinal cord injury (SCI) on the  peripheral sympathetic nerve, skin sympathetic activity (SSA), and muscle sympathetic activity (MSA). To  do this sixteen male Japanese white rabbits weighing 1.0 kg-1.5 kg were used. The exposed spinal cord was  transected at various levels. Microelectrodes were placed on the muscular branch and on the cutaneous  branch, and they were separately induced using a 0.5 -5 kHz amplifier. The data were calculated with the  time reset integration value at 60 seconds. Results: It is usually satisfactory to considered that the peripheral sympathetic fibers from T1-3 generally  pass up through the sympathetic chain to the upper extremities, and that fibers from T9-11 pass up through  the sympathetic chain to the lower limbs. In the electrophysiological properties studied, the SSA could not  be recognized as a spontaneous activity. On the other hand, the MSA could be recognized as a spontaneous  regular activity which synchronizes with the R wave of the electrocardiogram. Conclusions: The MSA potentials synchronized with the heart rate, and they seem to correlate with the  body homeostasis. The existence of a central regulatory mechanism is suggested from those findings not  only in vital rhythms, such as the heart rate variability but also in the MSA.

A Genome-Wide Association Analysis Identified a Novel Susceptible Locus for Pathological Myopia at 11q24.1

Myopia is one of the most common ocular disorders worldwide. Pathological myopia, also called high myopia, comprises 1% to 5% of the general population and is one of the leading causes of legal blindness in developed countries. To identify genetic determinants associated with pathological myopia in Japanese, we conducted a genome-wide association study, analyzing 411,777 SNPs with 830 cases and 1,911 general population controls in a two-stage design (297 cases and 934 controls in the first stage and 533 cases and 977 controls in the second stage). We selected 22 SNPs that showed P-values smaller than 10−4 in the first stage and tested them for association in the second stage. The meta-analysis combining the first and second stages identified an SNP, rs577948, at chromosome 11q24.1, which was associated with the disease (P = 2.22×10−7 and OR of 1.37 with 95% confidence interval: 1.21–1.54). Two genes, BLID and LOC399959, were identified within a 200-kb DNA encompassing rs577948. RT–PCR analysis demonstrated that both genes were expressed in human retinal tissue. Our results strongly suggest that the region at 11q24.1 is a novel susceptibility locus for pathological myopia in Japanese

Association of SIX1/SIX6 locus polymorphisms with regional circumpapillary retinal nerve fibre layer thickness: The Nagahama study

SIX1 and SIX6 are glaucoma susceptibility genes. Previous reports indicate that the single nucleotide polymorphism (SNP) rs33912345 in SIX6 is associated with inferior circumpapillary retinal nerve fibre layer (cpRNFL) thickness (cpRNFLT). Although the region of visual field defect in glaucoma patients is directly related to cpRNFL thinning, a detailed sector analysis has not been performed in genetic association studies. In the present study, we evaluated 26 tagging SNPs in the SIX1/SIX6 locus ±50 kb region in a population of 2, 306 Japanese subjects with 4- and 32-sector cpRNFLT analysis. While no SNPs showed a significant association with cpRNFLT in the 4-sectored analysis, the finer 32-sector assessment clearly showed a significant association between rs33912345 in the SIX1/SIX6 locus with inferior cpRNFL thinning at 292.5–303.8° (β = −4.55, P = 3.0 × 10−5). Furthermore, the fine-sectored cpRNFLT analysis indicated that SIX1/SIX6 polymorphisms would affect cpRNFL thinning at 281.3–303.8°, which corresponds to parafoveal scotoma in a visual field test of glaucoma patients

Association between the SERPING1 Gene and Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy in Japanese

PURPOSE: Recently, a complement component 1 inhibitor (SERPING1) gene polymorphism was identified as a novel risk factor for age-related macular degeneration (AMD) in Caucasians. We aimed to investigate whether variations in SERPING1 are associated with typical AMD or with polypoidal choroidal vasculopathy (PCV) in a Japanese population. METHODS: We performed a case-control study in a group of Japanese patients with typical AMD (n = 401) or PCV (n = 510) and in 2 independent control groups--336 cataract patients without age-related maculopathy and 1,194 healthy Japanese individuals. Differences in the observed genotypic distribution between the case and control groups were tested using chi-square test for trend. Age and gender were adjusted using logistic regression analysis. RESULTS: We targeted rs2511989 as the haplotype-tagging single nucleotide polymorphism (SNP) for the SERPING1 gene, which was reported to be associated with the risk of AMD in Caucasians. Although we compared the genotypic distributions of rs2511989 in typical AMD and PCV patients against 2 independent control groups (cataract patients and healthy Japanese individuals), SERPING1 rs2511989 was not significantly associated with typical AMD (P = 0.932 and 0.513, respectively) or PCV (P = 0.505 and 0.141, respectively). After correction for age and gender differences based on a logistic regression model, the difference in genotypic distributions remained insignificant (P>0.05). Our sample size had a statistical power of more than 90% to detect an association of a risk allele with an odds ratio reported in the original studies for rs2511989 for developing AMD. CONCLUSIONS: In the present study, we could not replicate the reported association between SERPING1 and either neovascular AMD or PCV in a Japanese population; thus, the results suggest that SERPING1 does not play a significant role in the risk of developing AMD or PCV in Japanese

CFHandVIPR2as susceptibility loci in choroidal thickness and pachychoroid disease central serous chorioretinopathy

中心性漿液性網脈絡膜症に関わる遺伝子変異を発見 --日本人に多い特殊なタイプの加齢黄斑変性の原因も解明--. 京都大学プレスリリース. 2018-05-31.Central serous chorioretinopathy (CSC) is a common disease affecting younger people and may lead to vision loss. CSC shares phenotypic overlap with age-related macular degeneration (AMD). As recent studies have revealed a characteristic increase of choroidal thickness in CSC, we conducted a genome-wide association study on choroidal thickness in 3, 418 individuals followed by TaqMan assays in 2, 692 subjects, and we identified two susceptibility loci: CFH rs800292, an established AMD susceptibility polymorphism, and VIPR2 rs3793217 (P = 2.05 × 10−10 and 6.75 × 10−8, respectively). Case–control studies using patients with CSC confirmed associations between both polymorphisms and CSC (P = 5.27 × 10−5 and 5.14 × 10−5, respectively). The CFH rs800292 G allele is reportedly a risk allele for AMD, whereas the A allele conferred risk for thicker choroid and CSC development. This study not only shows that susceptibility genes for CSC could be discovered using choroidal thickness as a defining variable but also, deepens the understanding of differences between CSC and AMD pathophysiology