論文 - 池田 康博
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Risk factors for posterior subcapsular cataract in retinitis pigmentosa 査読あり
Fujiwara K., Ikeda Y., Murakami Y., Funatsu J., Nakatake S., Tachibana T., Yoshida N., Nakao S., Hisatomi T., Yoshida S., Yoshitomi T., Ishibashi T., Sonoda K.
Investigative Ophthalmology and Visual Science 58 ( 5 ) 2534 - 2537 2017年5月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Investigative Ophthalmology and Visual Science
© 2017 The Authors. PURPOSE. Posterior subcapsular cataract (PSC) is a frequent complication in patients with retinitis pigmentosa (RP). The risk factors for PSC formation in RP are largely unknown. The purpose of this study was to investigate the risk factors for PSC. METHODS. We retrospectively studied a total of 322 eyes of 173 patients who were diagnosed with typical RP. We considered the following possible risk factors for PSC: age, sex, hypertension, diabetes mellitus, high myopia, asthma, history of steroid intake, and aqueous flare. Aqueous flare values were measured consecutively in 2012 and 2013 using a laser flare cell meter. The lens including PSC was examined with a slit lamp after dilation with tropicamide 1% and phenylephrine 2.5%. RESULTS. The geometric mean values of aqueous flare and mean values of visual acuity were significantly higher for the RP patients with PSC compared to those without PSC (P = 0.0003, P = 0.0004, respectively). When the aqueous flare values were assessed continuously, each 1-log-transformed increase in flare levels was associated with an elevation of the likelihood of having PSC after multivariable adjustment (odds ratio: 1.71; 95% confidence interval: 1.05-2.77). There were no significant associations of the other possible risk factors with PSC. CONCLUSIONS. Our analysis demonstrated that elevated aqueous flare is a significant risk factor for PSC formation. This result might provide insights into the association of inflammation and the pathogenesis of PSC formation in RP.
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Nakama T., Yoshida S., Ishikawa K., Kubo Y., Kobayashi Y., Zhou Y., Nakao S., Hisatomi T., Ikeda Y., Takao K., Yoshikawa K., Matsuda A., Ono J., Ohta S., Izuhara K., Kudo A., Sonoda K., Ishibashi T.
Molecular Therapy - Nucleic Acids 6 279 - 289 2017年3月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Molecular Therapy - Nucleic Acids
© 2017 Retinal neovascularization (NV) due to retinal ischemia remains one of the principal causes of vision impairment in patients with ischemic retinal diseases. We recently reported that periostin (POSTN) may play a role in the development of preretinal fibrovascular membranes, but its role in retinal NV has not been determined. The purpose of this study was to examine the expression of POSTN in the ischemic retinas of a mouse model of oxygen-induced retinal NV. We also studied the function of POSTN on retinal NV using Postn KO mice and human retinal endothelial cells (HRECs) in culture. In addition, we used a novel RNAi agent, NK0144, which targets POSTN to determine its effect on the development of retinal NV. Our results showed that the expression of POSTN was increased in the vascular endothelial cells, pericytes, and M2 macrophages in ischemic retinas. POSTN promoted the ischemia-induced retinal NV by Akt phosphorylation through integrin αvβ3. NK0144 had a greater inhibitory effect than canonical double-stranded siRNA on preretinal pathological NV in vivo and in vitro. These findings suggest a causal relationship between POSTN and retinal NV, and indicate a potential therapeutic role of intravitreal injection of NK0144 for retinal neovascular diseases.
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Kobayashi Y., Yoshida S., Zhou Y., Nakama T., Ishikawa K., Kubo Y., Arima M., Nakao S., Hisatomi T., Ikeda Y., Matsuda A., Sonoda K., Ishibashi T.
Laboratory Investigation 96 ( 11 ) 1178 - 1188 2016年11月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Laboratory Investigation
Tenascin-C is expressed in choroidal neovascular (CNV) membranes in eyes with age-related macular degeneration (AMD). However, its role in the pathogenesis of CNV remains to be elucidated. Here we investigated the role of tenascin-C in CNV formation. In immunofluorescence analyses, tenascin-C co-stained with α-SMA, pan-cytokeratin, CD31, CD34, and integrin α V in the CNV membranes of patients with AMD and a mouse model of laser-induced CNV. A marked increase in the expression of tenascin-C mRNA and protein was observed 3 days after laser photocoagulation in the mouse CNV model. Tenascin-C was also shown to promote proliferation and inhibit adhesion of human retinal pigment epithelial (hRPE) cells in vitro. Moreover, tenascin-C promoted proliferation, adhesion, migration, and tube formation in human microvascular endothelial cells (HMVECs); these functions were, however, blocked by cilengitide, an integrin α V inhibitor. Exposure to TGF-β2 increased tenascin-C expression in hRPE cells. Conditioned media harvested from TGF-β2-treated hRPE cell cultures enhanced HMVEC proliferation and tube formation, which were inhibited by pretreatment with tenascin-C siRNA. The CNV volume was significantly reduced in tenascin-C knockout mice and tenascin-C siRNA-injected mice. These findings suggest that tenascin-C is secreted by transdifferentiated RPE cells and promotes the development of CNV via integrin α V in a paracrine manner. Therefore, tenascin-C could be a potential therapeutic target for the inhibition of CNV development associated with AMD.
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Changes in chorioretinal blood flow velocity and cerebral blood flow after carotid endarterectomy 査読あり
Enaida H., Nagata S., Takeda A., Nakao S., Ikeda Y., Ishibashi T.
Japanese Journal of Ophthalmology 60 ( 6 ) 459 - 465 2016年11月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Japanese Journal of Ophthalmology
© 2016, Japanese Ophthalmological Society. Purpose: To investigate the changes in chorioretinal blood flow velocity and cerebral blood after carotid endarterectomy (CEA). Methods: Nine patients with moderate to severe internal carotid artery stenosis underwent CEA. Chorioretinal blood flow velocity was measured by laser speckle flowgraphy (LSFG), while cerebral blood flow (CBF) was measured by single-photon emission computed tomography (SPECT), on the affected side both before and after CEA. LSFG was evaluated in five areas to determine mean blur rate, while CBF was calculated from regional CBF and cerebrovascular reactivity (CVR), at the middle cerebral artery (MCA) region of each patient. Results: Five cases showed an increase (mean 3.49 %, range −29.82 to 35.59 %) of average chorioretinal blood flow velocity using LSFG after CEA. A particularly averaged increase in chorioretinal blood flow was observed in the macular area compared with other areas. Similarly, there was an increase in CBF at rest (mean 11.46 %, range −14.51 to 74.14 %) observed using SPECT after surgery. Improvement of CVR was confirmed in four cases. All general and visual symptoms disappeared after CEA. Severe adverse effects, including hyperperfusion syndrome, were not observed in any cases. Conclusions: LSFG may be useful for the analysis of chorioretinal blood flow changes after CEA.
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Yamaguchi M., Nakao S., Kaizu Y., Kobayashi Y., Nakama T., Arima M., Yoshida S., Oshima Y., Takeda A., Ikeda Y., Mukai S., Ishibashi T., Sonoda K.
Scientific Reports 6 2016年9月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Scientific Reports
Histological studies from autopsy specimens have characterized hard exudates as a composition of lipid-laden macrophages or noncellular materials including lipid and proteinaceous substances (hyaline substances). However, the characteristics of hard exudates in living patients have not been examined due to insufficient resolution of existing equipment. In this study, we used adaptive optics scanning laser ophthalmoscopy (AO-SLO) to examine the characteristics of hard exudates in patients with retinal vascular diseases. High resolution imaging using AO-SLO enables morphological classification of retinal hard exudates into two types, which could not be distinguished either on fundus examination or by spectral domain optical coherence tomography (SD-OCT). One, termed a round type, consisted of an accumulation of spherical particles (average diameter of particles: 26.9 ± 4.4 μm). The other, termed an irregular type, comprised an irregularly shaped hyper-reflective deposition. The retinal thickness in regions with round hard exudates was significantly greater than the thickness in regions with irregular hard exudates (P = 0.01 â †'0.02). This differentiation of retinal hard exudates in patients by AO-SLO may help in understanding the pathogenesis and clinical prognosis of retinal vascular diseases.
DOI： 10.1038/srep33574
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Koyanagi Y., Yoshida S., Kobayashi Y., Kubo Y., Yamaguchi M., Nakama T., Nakao S., Ikeda Y., Ohshima Y., Ishibashi T., Sonoda K.
Ophthalmologica 236 ( 2 ) 67 - 73 2016年9月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Ophthalmologica
© 2016 S. Karger AG, Basel. Copyright: All rights reserved. Purpose: To compare the effectiveness of intravitreal ranibizumab (IVR) for diabetic macular edema (DME) between eyes with and without previous vitrectomy. Procedures: We prospectively assessed the best-corrected visual acuity (BCVA) and central macular thickness (CMT) after IVR for 6 months. Results: There were no significant differences in the baseline BCVA and CMT between both groups. In the nonvitrectomized group (n = 15), the mean changes of BCVA and CMT from baseline to month 6 were significant (p < 0.01). In the vitrectomized group (n = 10), the improvement appeared to be slower, and the mean BCVA improvement was not significant (p = 0.5), although the mean CMT decrease was significant (p < 0.05). There were no significant differences in the mean changes of BCVA and CMT between both groups at 6 months. Conclusions: The difference in the effectiveness of IVR between both groups was not significant. IVR can be a treatment option even for vitrectomized DME eyes.
DOI： 10.1159/000446992
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Association between aqueous flare and epiretinal membrane in retinitis pigmentosa 査読あり
Fujiwara K., Ikeda Y., Murakami Y., Nakatake S., Tachibana T., Yoshida N., Nakao S., Hisatomi T., Yoshida S., Yoshitomi T., Sonoda K., Ishibashi T.
Investigative Ophthalmology and Visual Science 57 ( 10 ) 4282 - 4286 2016年8月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Investigative Ophthalmology and Visual Science
© 2016, Association for Research in Vision and Ophthalmology Inc. All rights reserved. PURPOSE. Epiretinal membrane (ERM) is a frequent macular complication in patients with retinitis pigmentosa (RP). The etiology of ERM formation in RP is largely unknown. The purpose of this study was to investigate the association between aqueous flare, a surrogate index of intraocular inflammation, and ERM secondary to RP. METHODS. We retrospectively studied a total of 206 eyes of 117 patients who were diagnosed with typical RP. Aqueous flare values were measured consecutively in 2012 and 2013 using a laser flare cell meter. Spectral-domain optical coherence tomography images and fundus photographs taken on the same day of the aqueous flare measurements were analyzed for ERM detection. RESULTS. The mean values of aqueous flare, age, and frequency of male sex were significantly higher in the RP patients with ERM compared with the RP patients without ERM (P < 0.0001, P = 0.007, and P = 0.004, respectively). After adjustment for age and sex, the eyes in the highest quartile of aqueous flare had significantly higher odds of having ERM than those in the lowest quartile (odds ratio [OR], 2.68; 95% confidence interval [CI], 1.04-6.93), and the linear trend across flare levels was significant (P = 0.005). In addition, each 1-log-transformed increase in flare values was associated with an elevation of the likelihood of having ERM (OR, 2.59; 95% CI, 1.33-5.06). CONCLUSIONS. Our analysis demonstrated that elevated aqueous flare is associated with ERM secondary to RP, suggesting that inflammation may be implicated in the pathogenesis of ERM formation in RP.
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Interleukin-12 inhibits pathological neovascularization in mouse model of oxygen-induced retinopathy 査読あり
Zhou Y., Yoshida S., Kubo Y., Kobayashi Y., Nakama T., Yamaguchi M., Ishikawa K., Nakao S., Ikeda Y., Ishibashi T., Sonoda K.
Scientific Reports 6 2016年6月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Scientific Reports
Hypoxia-induced retinal neovascularization is a major pathological condition in many vision-threatening diseases. In the present study, we determined whether interleukin (IL)-12, a cytokine that regulates angiogenesis, plays a role in the neovascularization in a mouse model of oxygen-induced retinopathy (OIR). We found that the expressions of the mRNAs of both IL-12p35 and IL-12p40 were significantly reduced in the OIR retinas compared to that of the room air-raised control. The sizes of the avascular areas and neovascular tufts were larger in IL-12p40 knock-out (KO) mice than that in wild type (WT) mice. In addition, an intravitreal injection of recombinant IL-12 reduced both avascular areas and neovascular tufts. IL-12 injection enhanced the expressions of interferon-gamma (IFN-γ) and other downstream chemokines. In an in vitro system, IL-12 had no significant effect on tube formation of human retinal microvascular endothelial cells (HRECs). Moreover, a blockade of IFN-γ suppressed the inhibitory effect of IL-12 on pathological neovascularization. These results suggest that IL-12 plays important roles in inhibiting pathological retinal neovascularization.
DOI： 10.1038/srep28140
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Kobayashi Y., Yoshida S., Zhou Y., Nakama T., Ishikawa K., Arima M., Nakao S., Sassa Y., Takeda A., Hisatomi T., Ikeda Y., Matsuda A., Sonoda K., Ishibashi T.
Molecular Vision 22 436 - 445 2016年4月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Molecular Vision
© 2016 Molecular Vision. Purpose: We previously demonstrated that tenascin-C was highly expressed in the fibrovascular membranes (FVMs) of patients with proliferative diabetic retinopathy (PDR). However, its role in the pathogenesis of FVMs has not been determined. The purpose of this study was to investigate what role tenascin-C plays in the formation and angiogenesis of FVMs. Methods: The level of tenascin-C was determined by sandwich enzyme-linked immunosorbent assay in the vitreous samples collected from patients with PDR and with a macular hole as control. The locations of tenascin-C, α- smooth muscle actin (SMA), CD34, glial fibrillary acidic protein (GFAP), and integrin αV in the FVMs from PDR patients were determined by immunohistochemistry. We also measured the in vitro expression of the mRNA and protein of tenascin-C in vascular smooth muscle cells (VSMCs) stimulated by interleukin (IL)-13. The effects of tenascin-C on cell proliferation, migration, and tube formation were determined in human retinal endothelial cells (HRECs) in culture. Results: The mean vitreous levels of tenascin-C were significantly higher in patients with PDR than in patients with a macular hole (p<0.001). Double immunofluorescence analyses of FVMs from PDR patients showed that tenascin-C co-stained FVMs with α-SMA, CD34, and integrin αV but not with GFAP. In addition, IL-13 treatment increased both the expression and secretion of tenascin-C by VSMCs in a dose-dependent manner. Tenascin-C exposure promoted proliferation, migration, and tube formation in HRECs. Tenascin-C neutralizing antibody significantly blocked the tube formation by HRECs exposed to VSMC-IL-13-conditioned medium. Conclusions: Our findings suggest that tenascin-C is secreted from VSMCs and promotes angiogenesis in the FVMs associated with PDR.
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MUTYH promotes oxidative microglial activation and inherited retinal degeneration 査読あり
Nakatake S., Murakami Y., Ikeda Y., Morioka N., Tachibana T., Fujiwara K., Yoshida N., Notomi S., Hisatomi T., Yoshida S., Ishibashi T., Nakabeppu Y., Sonoda K.H.
JCI Insight 1 ( 15 ) 2016年
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：JCI Insight
© 2016 American Society for Clinical Investigation. All rights reserved. Oxidative stress is implicated in various neurodegenerative disorders, including retinitis pigmentosa (RP), an inherited disease that causes blindness. The biological and cellular mechanisms by which oxidative stress mediates neuronal cell death are largely unknown. In a mouse model of RP (rd10 mice), we show that oxidative DNA damage activates microglia through MutY homolog–mediated (MUYTH-mediated) base excision repair (BER), thereby exacerbating retinal inflammation and degeneration. In the early stage of retinal degeneration, oxidative DNA damage accumulated in the microglia and caused single-strand breaks (SSBs) and poly(ADP-ribose) polymerase activation. In contrast, Mutyh deficiency in rd10 mice prevented SSB formation in microglia, which in turn suppressed microglial activation and photoreceptor cell death. Moreover, Mutyh-deficient primary microglial cells attenuated the polarization to the inflammatory and cytotoxic phenotype under oxidative stress. Thus, MUTYH-mediated BER in oxidative microglial activation may be a novel target to dampen the disease progression in RP and other neurodegenerative disorders that are associated with oxidative stress.
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Correlation between macular blood flow and central visual sensitivity in retinitis pigmentosa 査読あり
Murakami Y., Ikeda Y., Akiyama M., Fujiwara K., Yoshida N., Nakatake S., Notomi S., Nabeshima T., Hisatomi T., Enaida H., Ishibashi T.
Acta Ophthalmologica 93 ( 8 ) e644 - e648 2015年12月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Acta Ophthalmologica
© 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd. Purpose To investigate the changes in macular blood flow and the correlation between those changes and central visual function in patients with retinitis pigmentosa (RP). Methods The mean blur rate (MBR), a quantitative blurring index of the laser speckle pattern that represents retinal and choroidal blood flow, was measured by laser speckle flowgraphy. Mean blur rate values in the macular area were compared between 70 patients with RP and 28 control subjects. The relationships between MBR on the one hand and, on the other, visual acuity (VA), mean deviation (MD) and averaged macular sensitivity of static perimetry tests (Humphrey Filed Analyzer, the central 10-2 program) were analysed in patients with RP. Results Macular MBR was decreased to 75% in patients with RP compared with control subjects (p < 0.0001, Student's t-test). Spearman's rank testing showed that macular MBR was significantly correlated with VA (r = -0.261, p = 0.0299), MD values (r = 0.438, p = 0.0002) and averaged macular sensitivity at the central 4 and 12 points of static perimetry tests (r = 0.426 and 0.442, p = 0.0003 and 0.0002, respectively). Multivariable-adjusted analysis confirmed that MBR was independently associated with MD (p = 0.0002) and macular sensitivity at the central 4 and 12 points (p < 0.0001 and 0.0002, respectively). Conclusions Decreased macular blood flow was associated with reduced macular visual sensitivity in patients with RP. Although the cause-effect relationships remain to be elucidated, these findings suggest that vascular defects may be involved in the pathogenesis of RP such as central vision loss.
DOI： 10.1111/aos.12693
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Vitreous cysts in patients with retinitis pigmentosa 査読あり
Yoshida N., Ikeda Y., Murakami Y., Nakatake S., Tachibana T., Notomi S., Hisatomi T., Ishibashi T.
Japanese Journal of Ophthalmology 59 ( 6 ) 373 - 377 2015年11月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Japanese Journal of Ophthalmology
© 2015, Japanese Ophthalmological Society. Purpose: To determine the prevalence of vitreous cysts in patients with retinitis pigmentosa (RP). Methods: We retrospectively reviewed the charts of 435 consecutive patients diagnosed as having typical RP. Results: Vitreous cysts were diagnosed in 37 eyes of 28 patients with RP (13 males and 15 females; mean age 47.0 ± 19.8 years; range 15–79 years), for an overall prevalence of 6.4 %. The cysts were observed bilaterally in nine of the patients (32.1 %). Among these 28 patients, 11 (39.3 %) were younger than 40 years. In all, 81.8 % of the vitreous cysts were detected around the optic nerve head. Conclusions: We demonstrated that the prevalence of vitreous cysts was 6.4 % in patients with RP. These cysts were considered to be asymptomatic.
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Long-term surgical outcomes of epiretinal membrane in patients with retinitis pigmentosa 査読あり
Ikeda Y., Yoshida N., Murakami Y., Nakatake S., Notomi S., Hisatomi T., Enaida H., Ishibashi T.
Scientific Reports 5 2015年8月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Scientific Reports
Macular complications such as an epiretinal membrane (ERM), a cystoid macular edema and a macular hole lead to unexpected central vision impairment especially for patients with retinitis pigmentosa (RP). To evaluate the long-term surgical outcomes of pars plana vitrectomy (PPV) for ERM in patients with RP, we retrospectively reviewed the charts of a consecutive series of 10 RP patients who underwent PPV for ERM at Kyushu University Hospital. Visual acuity (VA) testing, a fundus examination, and an optical coherence tomography (OCT) analysis were conducted. The standard PPV using three sclerotomies was performed for ERM. PPV was performed in 12 eyes of 10 patients. One eye was excluded from the outcome assessment due to short period observation (18 months). There was no significantly deleterious change from the baseline to final VA between the operation eyes and the fellow eyes (P = 0.19). Moreover, morphological improvement was obtained in 9 of 11 eyes based on OCT. Our present data suggest that PPV may be tolerable in the management for ERM in RP patients over the long-term. Furthermore, the appearance of the ellipsoid zone was an important factor in the prediction of visual outcome and determination of surgical indication.
DOI： 10.1038/srep13078
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Relationship between aqueous flare and visual function in retinitis pigmentosa 査読あり
Murakami Y., Yoshida N., Ikeda Y., Nakatake S., Fujiwara K., Notomi S., Nabeshima T., Nakao S., Hisatomi T., Enaida H., Ishibashi T.
American Journal of Ophthalmology 159 ( 5 ) 958 - 963.e1 2015年5月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：American Journal of Ophthalmology
© 2015 by Elsevier Inc. All rights reserved. Purpose To investigate the correlation between aqueous flare values and central visual function in patients with retinitis pigmentosa (RP). Design Retrospective, observational case series. Methods We retrospectively studied 160 patients diagnosed with typical RP and 59 control subjects. Aqueous flare values were measured by laser flare cell meter. The relationships between aqueous flare and best-corrected visual acuity (VA) and mean deviation (MD) of static perimetry tests were analyzed in RP patients. Results The aqueous flare values were significantly higher in the RP patients compared to the control subjects (10.6 ± 7.9 vs 5.0 ± 2.1 photon counts per millisecond [pc/ms], P <.0001). In the RP patients, the aqueous flare values were negatively correlated with VA (r = 0.359, P <.0001) and MD (r = -0.330, P <.0001). Age-subgroup analysis showed a significant correlation between aqueous flare and VA in the RP patients' 40s, 50s, and 60s and between aqueous flare and MD in the 30s, 40s, 50s, and 60s. The RP patients with MD values ≥-15 decibels (dB) showed significantly higher levels of aqueous flare than those with MD values <-15 dB (12.0 ± 6.2 vs 8.7 ± 5.8, P =.0001). Conclusions Aqueous flare is increased in RP patients and negatively correlates with central visual function. These results suggest a close relationship between inflammation and central vision loss in RP.
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Factors affecting visual acuity after cataract surgery in patients with retinitis pigmentosa 査読あり
Yoshida N., Ikeda Y., Murakami Y., Nakatake S., Fujiwara K., Notomi S., Hisatomi T., Ishibashi T.
Ophthalmology 122 ( 5 ) 903 - 908 2015年5月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Ophthalmology
© 2015 American Academy of Ophthalmology. Purpose To investigate the factors affecting visual acuity after cataract surgery in patients with retinitis pigmentosa (RP). Design Retrospective, observational study. Participants We retrospectively reviewed the charts of a consecutive series of 40 patients with RP who underwent cataract surgery. Methods The changes in preoperative and postoperative best-corrected visual acuity (BCVA) were measured. We investigated the relation between preoperative mean deviation (MD) value on the Humphrey Field Analyzer (HFA: the central 10-2 program; Humphrey Instruments, Inc, San Leandro, CA) and final BCVA. We also investigated the relationship between preoperative ellipsoid zone (EZ; also called the inner/outer segment junction) conditions and final BCVA. In addition, we showed the prevalence of macular complications and capsule complications. Main Outcome Measures The BCVA, slit-lamp biomicroscopic analysis, visual field, and optical coherence tomography (OCT) were obtained. Results The mean of the BCVA significantly improved after cataract surgery from 0.76 (range, -0.08 to 2.30) to 0.45 (range, -0.18 to 2.00) (P < 0.005). However, final BCVA did not improve in 30 eyes (53.6%). The preoperative MD value and the final BCVA were significantly correlated, and the final BCVA significantly improved in the less advanced RP group (MD was >-15 decibels [dB]). The final BCVA was significantly better in the group in which preoperative OCT showed a normal EZ than in the groups in which the EZ was abnormal or not visible. Posterior capsular opacification was observed in 47 eyes (83.9%), and 23 eyes (41.1%) underwent YAG laser capsulotomy within a mean follow-up time of 3 years. Conclusions Final BCVA in approximately half of the eyes improved after cataract surgery in patients with RP. The preoperative ophthalmic examinations that may reflect macular (or foveal) function, such as HFA 10-2 program and OCT, are important parameters to assess postoperative visual outcome.
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Hisatomi T., Notomi S., Tachibana T., Oishi S., Asato R., Yamashita T., Murakami Y., Ikeda Y., Enaida H., Sakamoto T., Ishibashi T.
Retina 35 ( 2 ) 310 - 318 2015年2月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Retina
Copyright © by Ophthamic Communications Society. PURPOSE:: Brilliant Blue G is used as a surgical adjuvant for retinal surgery. Although BBG double or multiple staining was reported, the effectiveness and safety of repeated staining is still elusive. To further examine the effectiveness and safety, we examined BBG in clinical cases in vivo, primary cell culture in vitro, and surgically resected specimen ex vivo. METHODS:: A retrospective interventional case series with in vitro and ex vivo studies were performed. Vitrectomy was performed in 28 cases of epiretinal membrane with BBG single to multiple staining. The surgically resected membranes were stained by BBG with or without cellular fixation. Primary cell cultures were examined with BBG and live/death cell markers, such as Calcein AM and TUNEL. RESULTS:: Single staining provided satisfactory staining in seven cases. Double or multiple staining substantially visualized internal limiting membrane (21 cases), especially the edges of remaining internal limiting membrane (11 cases). Adverse retinal staining was not noted and the final visual acuity showed no difference with multiple staining. The live cells barely stained with BBG, while some dead cells were stained. CONCLUSION:: Brilliant Blue G multiple staining substantially enhanced the visualization of internal limiting membrane. The absence of abnormal staining supports the safety of repeated BBG staining.
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Proteomic study of retinal proteins associated with transcorneal electric stimulation in rats 査読あり
Kanamoto T., Souchelnytskyi N., Kurimoto T., Ikeda Y., Sakaue H., Munemasa Y., Kiuchi Y.
Journal of Ophthalmology 2015 2015年
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Ophthalmology
© 2015 Takashi Kanamoto et al. Background. To investigate how transcorneal electric stimulation (TES) affects the retina, by identifying those proteins up-and downregulated by transcorneal electric stimulation (TES) in the retina of rats. Methods. Adult Wistar rats received TES on the left eyes at different electrical currents while the right eyes received no treatment and served as controls. After TES, the eye was enucleated and the retina was isolated. The retinas were analyzed by proteomics. Results. Proteomics showed that twenty-five proteins were upregulated by TES. The identified proteins included cellular signaling proteins, proteins associated with neuronal transmission, metabolic proteins, immunological factors, and structural proteins. Conclusions. TES induced changes in expression of various functional proteins in the retina.
DOI： 10.1155/2015/492050
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Ikeda Y., Suzuki E., Kuramata T., Kozaki T., Koyama T., Kato Y., Murakami Y., Enaida H., Ishibashi T.
Japanese Journal of Ophthalmology 59 ( 1 ) 43 - 47 2015年
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Japanese Journal of Ophthalmology
© 2014, Japanese Ophthalmological Society. Purpose: Patients in the early stage of retinitis pigmentosa (RP) suffer from night blindness and, therefore, have mobility problems at night. To assist such patients with walking in the dark, we developed a wearable visual aid utilizing a see-through display upon which assistive images from a high-sensitivity video camera are superimposed. We evaluated the efficacy of our new visual aid for RP patients. Methods: The device is equipped with a camera with a minimum illuminance of 0.08 lux and a view angle of 53° × 40°. The experiment was conducted in a room with dimmed light (illuminance level 0.2–1.2 lux). Eight subjects with RP were instructed to arrive at a goal 16 m away from the starting point, both with and without the device, passing through four 1.5-m-wide gates consisting of pairs of black square carpet pieces, white poles, red and white traffic cones and cardboard boxes with and without the device in a darkened room. Three gates, except for the boxes, which were nearest the goal, were randomly arranged along the x-axis at each trial. The number of trial failures and the time required to walk the course were assessed as outcomes. Results: Seven of the 8 subjects could walk with the aid of the device without any failure. With the device, the number of trial failures significantly decreased in number (p < 0.05) in all subjects. Conclusions: This device enabled the subjects to see objects that could not be recognized by the unaided eye. Our visual aid effectively assisted RP patients with night blindness.
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Saadat K., Murakami Y., Tan X., Nomura Y., Yasukawa T., Okada E., Ikeda Y., Yanagi Y.
FEBS Open Bio 4 1007 - 1014 2014年12月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：FEBS Open Bio
© 2014 The Authors. In this study, we show augmented autophagy in the retinal pigment epithelial cell line ARPE-19 when cultured in the presence of the lipofuscin pigment A2E. A2E alone does not induce RPE cell death, but cell death was induced in the presence of A2E with the autophagy inhibitor 3-methyladenine (3MA), with a concomitant increase in the generation of mitochondrial reactive oxygen species. On the other hand, the ATP production capacity of mitochondria was decreased in the presence of A2E, and pharmacological inhibition of autophagy had no additional effects. The altered mRNA expression level of mitochondrial function markers was confirmed by real-time polymerase chain reaction, which showed that the antioxidant enzymes SOD1 and SOD2 were not reduced in the presence of A2E alone, but significantly suppressed with the addition of 3MA. Furthermore, transmission electron micrography revealed autophagic vacuole formation in the presence of A2E, and inhibition of autophagy resulted in the accumulation of abnormal mitochondria with loss of cristae. Spheroid culture of human RPE cells demonstrated debris accumulation in the presence of A2E, and this accumulation was accelerated in the presence of 3MA. These results indicate that autophagy in RPE cells is a vital cytoprotective process that prevents the accumulation of damaged cellular molecules.
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Hisatomi T., Notomi S., Tachibana T., Sassa Y., Ikeda Y., Nakamura T., Ueno A., Enaida H., Murata T., Sakamoto T., Ishibashi T.
American Journal of Ophthalmology 158 ( 3 ) 2014年9月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：American Journal of Ophthalmology
Purpose To investigate long-term ultrastructural changes in the retina after internal limiting membrane (ILM) peeling through the examination of morphologic changes 3 years after vitrectomy in cynomolgus monkeys. Design Laboratory investigation. Methods Pars plana vitrectomy was performed, followed by ILM peeling, in 2 primate eyes. Ultrastructural changes were investigated using light microscopy and transmission and scanning electron microscopy 3 years after ILM peeling. Results The remaining posterior vitreous and ILM-peeled areas were clearly recognized after the long-term follow-up. The exposed Müller cell processes were partially damaged, while regenerative spindle-shaped Müller cell processes developed, covering most of the retina. Notably, the nerve fiber layer was found to be uncovered and exposed to the vitreous space owing to misdirection of glial wound healing in some parts. In these areas, glial wound healing occurred beneath the nerve fiber layer. Although the glial cells covered the damaged areas, there was no apparent ILM regeneration in the shape of a continuous flat sheet, with the exception of accumulated deposits of basement membrane materials. Conclusions Although the retinal structures were well preserved after ILM peeling, ILM peeling resulted in mild damage to the vitreoretinal interface, which was not completely restored even after 3 years. The multilinear shape of the exposed nerve fiber may explain the previously reported dissociated optic nerve fiber layer appearance. The glial cells produced basement membrane materials around their processes, although they did not restore the ILM as a flat sheet. © 2014 by Elsevier Inc. All rights reserved.