Atsushi Minamoto

Intravitreal levels of vascular endothelial growth factor and interleukin-6 are correlated with macular edema in branch retinal vein occlusion

BackgroundTo investigate whether vascular endothelial growth factor (VEGF) or interleukin-6 (IL-6) contributes to the pathogenesis of macular edema in eyes with branch retinal vein occlusion (BRVO), the correlations between these factors were investigated.MethodsWe studied 25 patients suffering from macular edema with BRVO and 14 patients with nonischemic ocular disease (control group). The degree of retinal ischemia was evaluated in terms of the area of capillary nonperfusion using Scion Images, and the severity of macular edema was examined using optical coherence tomography. Vitreous fluid samples were obtained at the time of vitreoretinal surgery, and VEGF and IL-6 levels in the vitreous fluid and plasma were determined by means of enzyme-linked immunosorbent assays.ResultsVitreous fluid levels of VEGF and IL-6 were significantly elevated in patients with BRVO compared with control patients (P=0.0011 and P<0.0001, respectively). Also, the vitreous level of VEGF was significantly correlated with that of IL-6 (P=0.0012), and vitreous levels of VEGF and IL-6 were correlated with the size of the BRVO nonperfusion area (P<0.0001 and P=0.0033, respectively). Furthermore, vitreous levels of VEGF and IL-6 were correlated with the severity of macular edema (P=0.0008 and P=0.0191, respectively) and the severity of macular edema of BRVO was significantly correlated with the size of the BRVO nonperfusion area (P=0.0044).ConclusionsThe levels of VEGF and IL-6 are increased in patients with macular edema with BRVO and are significantly correlated with the size of the nonperfusion area and the severity of macular edema. Therefore, they may play a role in macular edema with BRVO.

Aqueous humour levels of cytokines are correlated to vitreous levels and severity of macular oedema in branch retinal vein occlusion

AimTo investigate whether the aqueous levels of vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) are correlated to the vitreous levels of these substances and to the severity of macular oedema in branch retinal vein occlusion (BRVO).MethodsAqueous and vitreous samples were obtained during cataract and vitreous surgery from 24 patients (24 eyes) with macular oedema in BRVO. The VEGF and IL-6 levels in aqueous humour, vitreous fluid, and plasma were determined by enzyme-linked immunosorbent assay. The degree of retinal ischaemia was evaluated in terms of the area of capillary nonperfusion using the Scion Image. The severity of macular oedema was evaluated using the OCT.ResultsThe aqueous level of VEGF was significantly correlated with the vitreous level of VEGF (P<0.0001). Vitreous levels of VEGF and IL-6 were significantly correlated with the nonperfusion area of BRVO (P<0.0001, P=0.0061, respectively), as were the aqueous levels of VEGF and IL-6 (P<0.0001, P=0.0267, respectively). Furthermore, the vitreous levels of VEGF and IL-6 and the aqueous level of VEGF were significantly correlated with the severity of macular oedema of BRVO (P=0.0001, P=0.0331, P=0.0272, respectively).ConclusionOur results suggest that the aqueous level of VEGF may reflect its vitreous level. Measurement of the aqueous level of VEGF may be clinically useful to indicate the severity of macular oedema with BRVO.

Postoperative Cataract Cases among Atomic Bomb Survivors: Radiation Dose Response and Threshold

Abstract Neriishi, K., Nakashima, E., Minamoto, A., Fujiwara, S., Akahoshi, M., Mishima, H. K., Kitaoka, K. and Shore, R. E. Postoperative Cataract Cases among Atomic Bomb Survivors: Radiation Dose Response and Threshold. Radiat. Res. 168, 404–408 (2007). Recent evidence argues against a high threshold dose for vision-impairing radiation-induced cataractogenesis. We conducted logistic regression analysis to estimate the dose response and used a likelihood profile procedure to determine the best-fitting threshold model among 3761 A-bomb survivors who underwent medical examinations during 2000–2002 for whom radiation dose estimates were available, including 479 postoperative cataract cases. The analyses indicated a statistically significant dose–response increase in the prevalence of postoperative cataracts [odds ratio (OR), 1.39; 95% confidence interval (CI), 1.24–1.55] at 1 Gy, with no indication of upward curvature in the dose response. The dose response was suggestive when the restricted dose range of 0 to 1 Gy was examined. A nonsignificant dose threshold of 0.1 Gy (95% CI, <0–0.8) was found. The prevalence of postoperative cataracts in A-bomb survivors increased significantly with A-bomb radiation dose. The estimate (0.1 Gy) and upper bound (0.8 Gy) of the dose threshold for operative cataract prevalence was much lower than the threshold of 2–5 Gy usually assumed by the radiation protection community and was statistically compatible with no threshold at all.

A Reanalysis Of Atomic-bomb Cataract Data, 2000–2002: A Threshold Analysis

To obtain the best statistical model for a previous study of cataract prevalence in atomic-bomb survivors, we tested the fitness of the threshold model in an updated dataset of the study, utilizing re-diagnosis by a single ophthalmologist, use of the DS02 dosimetry system, and separation of the in utero group. The results suggest that, in 730 atomic-bomb survivors, we cannot conclude thresholds are greater than 0 Sv in cortical cataract and posterior sub-capsular opacity since the lower 90% confidence limits of the thresholds were 0 Sv. Threshold dose point estimates were 0.6 Sv (90% CI, <0.0–1.2 Sv) and 0.7 Sv (90% CI, <0.0–2.8 Sv) for cortical cataract and posterior sub-capsular opacity, respectively. Detailed regression analyses with no threshold model showed that nuclear color and nuclear opacity have no dose responses (p > 0.40). Cortical cataract showed a significant dose effect (p = 0.002), with an odds ratio (OR)/Sv of 1.30 (95% CI, 1.10–1.53) and no dose-effect modifiers. Posterior sub-capsular opacity showed a significant dose effect (p < 0.001), with an OR/Sv of 1.44 at age of exposure of 10 y (95% CI, 1.19–1.73). The dose effect decreased significantly with increasing age at exposure (p = 0.022). No dose response was observed for in utero survivors (p > 0.20).

Cataract in atomic bomb survivors.

Purpose: Ophthalmologic examinations were conducted on atomic bomb (A‐bomb) survivors 55 years after exposure. Materials and methods: A‐bomb survivors who had been exposed before 13 years of age at the time of the bombings in 1945 or who had been examined in a previous study between 1978 and 1980. The examinations, conducted between June 2000 and September 2002, included slit‐lamp examination, digital photography and a cataract grading system for three parts of the lens (nucleus, cortex and posterior subcapsule) as an outcome variable. Proportional odds logistic regression analysis was conducted using the lowest grading class as a reference and included explanatory variables such as age, sex, city, dose and various cataract‐related risk factors. When the grades in an individual differed, the worst grade was used. Results: Results indicate that odds ratios (ORs) at 1 Sv were 1.07 (95% confidence intervals [CI] 0.90, 1.27) in nuclear colour, 1.12 (95% CI 0.94, 1.30) in nuclear cataract, 1.29 (95% CI 1.12, 1.49) in cortical cataract and 1.41 (95% CI 1.21, 1.64) in posterior subcapsular cataract. The same was true after excluding 13 people whose posterior subcapsular cataracts had been previously detected. Conclusion: Significant radiation effects were observed in two types of cataracts in A‐bomb survivors.

Proteome Analysis of Human Vitreous Proteins

Purpose: Various protein contents such as enzymes, growth factors, and structural components are responsible for biological activities in organs. We have created a map of vitreous proteins and developed a proteome analysis of human vitreous samples to understand the underlying molecular mechanism and to provide clues to new therapeutic approaches in eyes with proliferative diabetic retinopathy (PDR). Methods: Vitreous and serum samples were obtained from subjects with idiopathic macular hole (MH, 26 cases) and PDR (33 cases). The expressed proteins in the samples were separated by two-dimensional (2-D) polyacrylamide gel electrophoresis. Protein spots were visualized by silver staining, and their expression patterns were analyzed. Some protein spots of concern were excised from the 2-D gels, digested in situ with trypsin, and analyzed by mass spectrometry. Results: More than 400 spots were detected on 2-D gels of MH cases, of which 78 spots were successfully analyzed. The spots corresponded to peptide fragments of 18 proteins, including pigment epithelium-derived factor, prostaglandin-D2 synthase, and interphotoreceptor retinoid-binding protein. These were not identified in the corresponding serum samples. These proteins were also expressed in PDR samples, with no distinct tendency to increase or decrease compared with the MH samples. More than 600 spots were detected on 2-D gels of PDR cases, of which 141 spots were successfully analyzed. The spots corresponded to peptide fragments of 38 proteins. Enolase and catalase were identified among four detected spots. Neither was found in MH vitreous or in PDR serum samples. Conclusion: A map of protein expression was made in human vitreous from eyes with MH and PDR. In the PDR eyes, the increased protein expression observed was due to barrier dysfunction and/or production in the eye. Proteome analysis was useful in systematic screening of various protein expression in human vitreous samples.

No Association Of Complement Factor H Gene Polymorphism And Age-related Macular Degeneration In The Japanese Population

Purpose: The aim of this study was to determine whether genetic polymorphism of complement factor H (CFH) is associated with age-related macular degeneration (AMD) in the Japanese population. Methods: Genomic DNA was examined in a cohort of 67 Japanese patients with AMD and 107 controls. TT/TC/CC genotypes on exon 9 were screened for sequence alternation by polymerase chain reaction analysis and through sequencing. Results: The mean ages ± SD of AMD patients and control subjects were 73 ± 8.5 years and 72 ± 8.7 years, respectively. There was no significant difference between CFH genotypes in the AMD group (TT, 76%; TC, 19%; CC, 5%) and the control group (TT, 80%; TC, 17%; CC, 3%). The frequencies of T and C alleles were 86% and 14%, respectively, in the AMD group and 89% and 11%, respectively, in the control group. Conclusion: CFH gene polymorphism is not associated with AMD in the Japanese population. Moreover, the frequency of the C allele is low among the Japanese population.

Neuroprotective effects of erythropoietin on glutamate and nitric oxide toxicity in primary cultured retinal ganglion cells

Erythropoietin receptor (EpoR) is expressed in the central nervous system (CNS), however, no clear consensus has been obtained whether Epo acts as a prosurvival factor in neurons. Because retinal ganglion cell (RGC) death is a common cause of reduced visual function in several ocular diseases, we explored whether Epo might potentially be beneficial in protecting RGCs from glutamate and nitric oxide (NO)-induced cytotoxicity, using isolated RGCs by a two-step panning method. Brain-derived neurotrophic factor (BDNF) was used as a positive control. EpoR mRNA was expressed in isolated RGCs, and EpoR protein was expressed on the RGCs in the normal and ischemic retinas. Epo had less potential to improve the survival of primary RGCs in serum-free medium than BDNF. In these cells, BDNF, but not Epo, downregulated the expression of Bim, a proapoptotic Bcl-2 family member that plays a key role in cytokine-mediated cell survival, suggesting a possible mechanism for this difference. When RGCs were cultured with glutamate or an NO-generating reagent, the survival of RGCs was compromised, and Bcl-2 expression was decreased in these cells. Both Epo and BDNF significantly reduced RGC death induced by glutamate and NO. In agreement with this, these factors reversed the Bcl-2 expression. These findings suggest that Epo may be a potent neuroprotective therapeutic agent for the treatment of ocular diseases that are characterized by RGC death.

Radiation Cataractogenesis: Epidemiology and Biology

a Lawrence Berkeley National Laboratory, Berkeley, California; b Columbia University, New York, New York; c Radiation Effects Research Foundation, Hiroshima, Japan; d National Cancer Institute, Bethesda, Maryland and The Maccabi Institute for Health Services Research, Tel Aviv, Israel; e Brigham and Women’s Hospital, Boston, Masschusetts; f Lyndon B. Johnson Space Center, NASA, Houston, Texas; g Minamoto Eye Clinic, Hiroshima, Japan; h Nagasaki University, Nagasaki, Japan; i Hiroshima University, Hiroshima, Japan; j SRI International, Menlo Park, California; and k Research Reactor Institute, Kyoto University, Japan

Characteristics and surgical outcomes of paediatric retinal detachment

AbstractPurpose To report the clinical features and surgical and visual outcomes of rhegmatogenous retinal detachment (RRD) in the paediatric population.Methods A retrospective review of children (aged 0–15 years) who underwent primary surgical repair for RRD at the Hiroshima University Hospital between 1988 and 2001.Results In all 53 eyes of 49 patients were identified; paediatric RRD accounted for 3.1% of 1779 eyes with RRD operated on during this period. The causes of RRD included blunt trauma (27%), myopia (25%), idiopathic (20%), familial exudative vitreoretinopathy (13%), and others. Among 55 eyes, 12 (22%) already had proliferative vitreoretinopathy (PVR) of grade C or D preoperatively. The median initial visual acuity (VA) was 0.3. Retinal reattachment was achieved with a single operation in 78%. Final retinal reattachment was achieved in 87%. Retinal reattachment rates with and without PVR were 42% and 100%, respectively (P<0.01). Median final VA was 0.7. Final VA was ⩾0.1 in 73% and ⩾0.5 in 53%; four eyes had a final VA of no light perception. The presence of preoperative PVR (P=0.03) and the initial VA (P<0.0001) significantly affected final VA.Conclusions Paediatric RRD is characterised by a delay in diagnosis, as evidenced by the high rate of PVR at presentation. Retinal reattachment was adversely affected by the presence of PVR. Final VA correlated with the initial VA and was significantly affected by preoperative PVR. Early diagnosis may improve the visual prognosis of paediatric retinal detachment.