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Hirokazu Sakaguchi

Publications and source records attributed to Hirokazu Sakaguchi.

At least 19 recordsLinked to original sources
PubMed2006

Regression of iris neovascularization after intravitreal injection of bevacizumab in patients with proliferative diabetic retinopathy.

PURPOSE: To assess the short-term safety and efficacy of intravitreal injection of bevacizumab for iris neovascularization (INV). DESIGN: Noncomparative, interventional case series. METHODS: Intravitreal bevacizumab was injected in seven eyes of five patients with INV that was associated with proliferative diabetic retinopathy (PDR). The main outcome measurements were visual acuity, intraocular pressure (IOP), and regression of INV by fluorescein angiography before and one week, one month, and two months after injection. RESULTS: Regression of INV was confirmed in all eyes (100%) from one week after injection. Repeated injections stabilized the recurrence (two eyes; 29%) that was observed two months after the initial injection. The visual acuity remained stable or improved, and the intraocular pressure was controlled in six eyes (86%) throughout the follow-up period. No inflammation or complications were observed. CONCLUSIONS: Intravitreal injection of bevacizumab may be an effective and safe alternative for patients with INV that is refractory to conventional treatments.

Adult↗
PubMed2006

Preparation and characterization of stimuli-resistible hydrogels nano-coated with polyelectrolyte multilayer films.

Alginate (ALG) hydrogels were nano-coated with polyelectrolyte multilayer (PEM) films composed of poly(diallyldimethyl ammonium chloride) (PDDA) and poly(sodium 4-styrenesulfonate) (PSS). Non- and nano-coated ALG hydrogels were immersed into salt solutions (pH 6, ionic strength: 0.01 M), and the swelling behavior of these ALG hydrogels was observed by optical microscopy. The increases in the diameter of the 10-step coated ALG hydrogels were one fourth or less than that of the non-coated hydrogels. These results indicate that the characteristics of nano-coated ALG hydrogels remain unchanged independent of how the external environment is changed (e.g., pH, ionic strength). Consequently, tolerant ionic hydrogels may be prepared by the nano-coating of hydrogel surfaces with PEM films and may be useful for technological and biomedical applications.

Absorption↗
PubMed2006

[Sub-Tenon's injection of triamcinolone acetonide for choroidal neovascularization].

PURPOSE: To evaluate the efficacy of sub-Tenon's injection of triamcinolone acetonide for age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). METHOD: Sub-Tenon's injection of triamcinolone acetonide was performed in patients (27 eyes) with the subfoveal choroidal neovascularization of AMD and in patients (10 eyes) with PCV, and its efficacy was evaluated. The visual acuity and the exudation from lesions evaluated by fluorescein angiography or optical coherence tomography (OCT) at three months or six months after injection were compared to the baseline values. RESULTS: Visual acuity was maintained in 23 of the 27 eyes (85.0%) with AMD and in 8 of the 10 eyes (80.0%) with PCV at three months after injection. Six months after infusion, the rate declined to 76.0% and 66.7%, respectively. Exudation from lesions had decreased in 10 eyes of 25 eyes(40.0%) with AMD and in 2 eyes of 9 eyes (22.2%) with PCV by six months after injection. Complete suppression of the lesions was observed in seven eyes (18.9%) with relatively small lesions. CONCLUSION: Sub-Tenon's injection of triamcinolone acetonide is useful as a treatment modality for AMD and PCV.

Aged↗
PubMed2005

Electrophysiological and histological studies of chronically implanted intrapapillary microelectrodes in rabbit eyes.

PURPOSE: To determine the safety and efficacy of transsclerally placed intrapapillary wire microelectrodes implanted chronically into the optic nerve head of rabbit eyes. METHODS: Four platinum wire microelectrodes were passed through the sclera and implanted into the optic nerve head of five rabbit eyes for 4-6 months. Color fundus photography, fluorescein angiography, electroretinograms (ERGs), and visually evoked potentials (VEPs) were used to monitor the retina. Electrically evoked potentials (EEPs) were elicited by bipolar electrical stimulation of the optic nerve axons by different combinations of the four electrodes immediately after the implantation and at 1-month intervals thereafter. The effects of the chronic implantation of the electrodes on the morphology of the optic nerve were evaluated by histological and immunohistochemical examinations at 4 and 6 months after the implantation. RESULTS: All of the electrodes remained stable in the implanted sites throughout the post-implantation period, except for one electrode that had pulled out of the optic nerve head at 1 month after implantation. No intraocular infection, inflammation, or vitreoretinal proliferation was observed in any eye. EEPs could be elicited from each pair of electrodes at all testing times. The mean threshold currents (charge densities) to evoke EEPs increased from 19.3 +/- 9.2 microA (6.0 +/- 2.9 microC/cm2) on the implantation day to 78.8 +/- 31.9 microA (24.6 +/- 10.0 microC/cm2) at 1 month after implantation, but did not change significantly thereafter. The implicit time and amplitude of the a- and b-waves of the ERGs and of P1 of the VEPs did not change significantly throughout the post-implantation period. Histological evaluation of the optic nerve head revealed slight tissue encapsulations surrounding the electrode and increased expression of glial fibrillary acidic protein near the surface of the optic nerve. CONCLUSIONS: Implantation of transscleral intrapapillary microelectrodes appears to be safe and effective. These findings indicate that the implantation of microelectrodes in the optic nerve head should be considered for an optic nerve-based prosthesis.

Animals↗
PubMed2005

New micro vertical scissors for the surgical ablation of retinal angiomatous proliferation.

PURPOSE: To develop new micro vertical scissors for the ablation of retinal angiomatous proliferation (RAP) to minimize possible retinal damage. DESIGN: Interventional case report. METHODS: New micro vertical scissors were developed and used for the ablation of RAP vessels. RESULTS: The length of the inner side of the tip is 180 microm, which is approximately one seventh that of regular vertical scissors. The scissors handled easily and the RAP vessels were ablated with less retinal damage compared with that associated with use of standard vertical scissors. Postoperatively, intraretinal hemorrhage was reduced and hyperfluorescence seen on indocyanine green angiography resolved. CONCLUSIONS: The new micro vertical scissors developed for the ablation of RAP vessels can be used safely and effectively during this surgical procedure.

Aged↗
PubMed2005

Recurrent retinal angiomatous proliferation after surgical ablation.

PURPOSE: To report a case of retinal angiomatous proliferation (RAP) treated by ablation of the feeding and draining vessels that recurred by 6 months postoperatively. DESIGN: Interventional case report. METHODS: Images from fluorescein angiography, indocyanine green (ICG) angiography, and optical coherence tomography (OCT) were examined before and after ablation. RESULTS: The hot spot on late-phase ICG, the leakage on fluorescein angiography, the pigment epithelial detachment, and macular edema on OCT decreased postoperatively. However, a large hyperfluorescent lesion was detected on ICG 6 months postoperatively with recurrent cystoid macular edema. CONCLUSIONS: A new RAP lesion can develop even after the original lesion seemed to resolve after ablation.

Aged↗
PubMed2005

Nonvitrectomizing vitreous surgery for epiretinal membrane long-term follow-up.

PURPOSE: To report the long-term follow-up results of nonvitrectomizing vitreous surgery for idiopathic epiretinal membrane (ERM). DESIGN: Nonrandomized comparative case series. PARTICIPANTS: Thirty patients were followed up for at least 5 years after nonvitrectomizing vitreous surgery. INTERVENTION: Epiretinal membranes were peeled without infusion of balanced salt solution and removal of the vitreous. The data from the fellow eye was the control data. MAIN OUTCOME MEASURES: We examined the visual acuities (VAs), objective refractions, and slit-lamp and Scheimpflug photographs from the preoperative and the final examinations of both eyes. Quantitative assessment of the progression of nuclear sclerosis was performed by densitometry analysis using Scheimpflug photography. The recurrence rate of ERM was determined. RESULTS: The follow-up periods ranged from 60 to 102 months (mean+/-standard deviation, 72.2+/-11.0 months). The patient ages ranged from 52 to 76 years (68.8+/-6.3 years). The final VA improved or stabilized within 2 lines in 29 of 30 eyes (96.7%). No unilateral progression of nuclear sclerosis occurred in any cases. The mean preoperative and postoperative refractions without additional surgery were -0.4+/-2.9 diopters (D) and -0.2+/-3.0 D in the operated eyes, respectively, and -0.2+/-2.5 D and 0.1+/-2.4 D, respectively, in the unoperated fellow eyes. The mean differences in the refractive error between both eyes (operated eye data minus fellow eye data) were -0.2+/-0.7 D before surgery and -0.3+/-0.8 D after surgery (P = 0.319, paired t test). The mean preoperative and postoperative nuclear densities in 16 patients were 69+/-14 nuclear density units (NDUs) and 76+/-12 NDUs in the operated eyes and 71+/-14 NDUs and 78+/-14 NDUs in the fellow eyes, respectively. The mean preoperative and postoperative differences in nuclear densities in both eyes were -2+/-2 NDUs and -2+/-5 NDUs, respectively (P = 0.836, paired t test). The ERM recurred in 10 eyes (33%), and 3 eyes underwent conventional vitrectomy combined with cataract surgery. CONCLUSIONS: Unilateral nuclear sclerosis did not progress for at least 5 years after nonvitrectomizing vitreous surgery. The recurrence rate of ERM appeared to be higher than that after conventional vitreous surgery.

Aged↗
PubMed2004

Transretinal electrical stimulation by an intrascleral multichannel electrode array in rabbit eyes.

BACKGROUND: A new method of stimulating the retina electrically, called suprachoroidal transretinal stimulation (STS), was shown to be effective in eliciting electrically evoked cortical potentials (EEPs) in Royal College of Surgeons (RCS) rats. Before extending this technique to patients, it is important to determine its safety and feasibility in eliciting EEPs from medium-size animal (rabbits). The purpose of this study was to determine the safety and efficacy of the surgical procedures used to implant an multichannel electrode array into a scleral pocket, and to determine whether the implanted electrodes can stimulate the retina effectively. METHODS: These acute experiments were conducted on six rabbits. An array of eight gold microelectrodes, embedded in polyimide, was implanted into a scleral pocket over the visual streak area. The size of the microarray was 2 x 4 x 0.180 mm. The reference electrode was implanted into the vitreous. The electrode array and reference electrodes were connected to a stimulator to deliver monophasic current pulses. Cortical responses were recorded with a stainless steel electrode implanted into each rabbit's skull over the visual cortex. After the experiment, the eyes and electrodes were examined histologically. RESULTS: The surgical procedures for electrode implantation were accomplished without serious complications. EEPs were recorded after monophasic electrical pulse stimulation from each electrode. The mean threshold for EEPs was 55.0+/-10.0 microA with a 0.5-ms duration inward current pulse. The charge delivered at threshold was about 27.5 nC, and the charge density was about 56.0 microC/cm2. Histopathological examination of the retinal tissue around the area of stimulation did not show damage at the light microscope level with the electrical parameters used. CONCLUSIONS: Our technique for STS with an intrascleral microelectrode array is safe in rabbit eyes, and EEPs were elicited by current densities that did not induce tissue damage. These results suggest that STS via intrascleral multichannel electrodes is a feasible method for stimulating the retina.

Animals↗
PubMed2004

Direct stimulation of optic nerve by electrodes implanted in optic disc of rabbit eyes.

PURPOSE: To determine whether wire microelectrodes implanted in the optic disc can be used to elicit cortical potentials. METHODS: Two or four platinum wire electrodes of two types, viz., the cut-end type and the exposed-tip type, were inserted through the vitreous and fixed in the optic disc of 16 rabbit eyes. Electrically evoked potentials (EEPs) were recorded after bipolar electrical stimulation with the two wire electrodes and by different combinations of the four-electrode system. The optic discs were examined histologically after the experiment. RESULTS: The wire electrodes were successfully implanted and fixed into different positions of the optic disc without serious complications in all 16 eyes. EEPs could be elicited after bipolar electrical stimulation of the optic nerve using either the two-electrode system or different pairs of the four-electrode system. Threshold charge densities to elicit EEPs were 0.32-0.64 mC/cm(2) in eyes using the cut-end type of electrodes and 0.93-6.21 muC/cm(2) in eyes using the exposed-tip type. The amplitude of the EEPs increased with increasing electrical stimulus intensities. Histological evaluation revealed limited damage to the neural tissue adjacent to the electrode track. CONCLUSIONS: The visual cortex can be activated by direct microelectrical stimulation of the optic nerve. The acute implantation of the wire microelectrodes into the optic disc by a transvitreal approach is feasible and results in only limited damage to the optic nerve.

Animals↗
PubMed2004

Multiple components of epiretinal tissues detected by triamcinolone and indocyanine green in macular hole and retinal detachment as a result of high myopia.

PURPOSE: To examine three layers of membranes detected by triamcinolone acetonide (TA) and indocyanine green (ICG) during surgery for macular hole and retinal detachment (MHRD) as a result of high myopia. DESIGN: Histologic study. METHODS: We excised three layers of membranes visualized with TA and ICG that were tightly adhering to the retinal surface during vitrectomy and examined them by transmission electron microscopy. RESULTS: The first membrane was made of acellular collagen fibers, suggestive of vitreous, and the second was comprised of parts of fibroblast-like cells and collagen fibrils, suggesting a proliferative epiretinal membrane. The third membrane was an internal limiting membrane. CONCLUSIONS: Multiple components of epiretinal tissue could be delaminated with the assistance of TA and ICG during surgery for myopic MHRD.

Aged↗
PubMed2004

Nonaxoplasmic transfer of indocyanine green into the optic nerve after intravitreal application.

PURPOSE: To investigate whether indocyanine green (ICG) migrates into the optic nerve after intravitreal application in the rabbit eye. METHODS: Gas vitrectomy was performed in one eye of adult Dutch belted rabbits by pars plana injection of 0.4 ml of 100% C3F8 (n = 10). One week later, vitrectomy was performed and 0.2 ml of 0.25% ICG was instilled into the vitreous cavity of these vitrectomized eyes. After 30 seconds of ICG application, the vitreous cavity was rinsed with balanced salt solution plus. Unoperated rabbits served as controls (n = 2). Globes, optic nerves, and the entire brain were removed, and ICG fluorescence of the specimens was examined with a digital fundus camera starting from the first day to the fourth postoperative week. Other rabbit eyes (n = 2) were injected with ICG directly into the vitreous without vitrectomy, and assessed for ICG signal after 1 day of ICG application. In the second part of the experiment, four rabbit eyes were gas vitrectomized and ICG was instilled onto retina after blockage of axonal flow by vinblastine. They were evaluated on the first (n = 2) and seventh postoperative days (n = 2). RESULTS: No fluorescein was detected in the visual pathways and the brains of the control group of rabbits. The optic nerves of the ICG-instilled eyes were stained diffusely with ICG starting from the first day after surgery. ICG injected nonvitrectomized eyes showed similar ICG staining patterns when compared with vitrectomized eyes. ICG staining pattern of the optic nerve did not differ in vinblastine-pretreated eyes. Fluorescence extended along the intraorbital portion of the optic nerve but did not transport more posteriorly in all animals. At the fourth week after vitrectomy, ICG signal was still detectable, but staining was less intense. CONCLUSION: Intravitreal ICG injection results in nonaxoplasmic extension into the optic nerve in the rabbit.

Animals↗
PubMed2003

Intense light exposure changes the crystallin content in retina.

Toward a better understanding of light-induced photoreceptor damage, the crystallin content of rat retina was examined following intense light exposure. Nine crystallin species were identified by mass spectrometric analysis of rat retina fractionated by 2D gel electrophoresis. The Coomassie blue staining intensity of all crystallin 2D gel components was 2- to 3-fold greater in light exposed than in control retinas. Following light exposure, anti-alphaB-crystallin immunoreactivity was increased in rod outer segments and retinal pigment epithelium. These findings support a possible role for crystallins in protecting photoreceptors from light damage.

Animals↗
PubMed2002

Drusen proteome analysis: an approach to the etiology of age-related macular degeneration.

Drusen are extracellular deposits that accumulate below the retinal pigment epithelium on Bruch's membrane and are risk factors for developing age-related macular degeneration (AMD). The progression of AMD might be slowed or halted if the formation of drusen could be modulated. To work toward a molecular understanding of drusen formation, we have developed a method for isolating microgram quantities of drusen and Bruch's membrane for proteome analysis. Liquid chromatography tandem MS analyses of drusen preparations from 18 normal donors and five AMD donors identified 129 proteins. Immunocytochemical studies have thus far localized approximately 16% of these proteins in drusen. Tissue metalloproteinase inhibitor 3, clusterin, vitronectin, and serum albumin were the most common proteins observed in normal donor drusen whereas crystallin was detected more frequently in AMD donor drusen. Up to 65% of the proteins identified were found in drusen from both AMD and normal donors. However, oxidative protein modifications were also observed, including apparent crosslinked species of tissue metalloproteinase inhibitor 3 and vitronectin, and carboxyethyl pyrrole protein adducts. Carboxyethyl pyrrole adducts are uniquely generated from the oxidation of docosahexaenoate-containing lipids. By Western analysis they were found to be more abundant in AMD than in normal Bruch's membrane and were found associated with drusen proteins. Carboxymethyl lysine, another oxidative modification, was also detected in drusen. These data strongly support the hypothesis that oxidative injury contributes to the pathogenesis of AMD and suggest that oxidative protein modifications may have a critical role in drusen formation.

Aged↗
PubMed2002

Claudin localization in cilia of the retinal pigment epithelium.

Using immunocytochemistry and confocal microscopy we demonstrate that claudin-immunoreactivity is a novel marker for retinal pigment epithelial cilia. Claudin-immunoreactivity obtained by polyclonal anti-claudin 1 antibody, which could crossreact with claudin 3, was colocalized with acetylated tubulin-immunoreactivity in cultured human retinal pigment epithelial cells. Claudin-immunoreactivity associated with the retinal pigment epithelium (RPE) cilia was more intense than was claudin-immunoreactivity in the junctional complex. Approximately two-thirds of the RPE cells in the rat contain cilia that are immunoreactive with acetylated tubulin on postnatal day 1, and a significant portion of these cilia label with the anti-claudin 1 antibody. Cilia decrease in frequency over subsequent postnatal days, and are absent by postnatal day 30. As RPE cilia decrease in number during postnatal rat development, claudin-immunoreactivity is lost earlier than acetylated tubulin, suggesting that the loss of claudin may initiate RPE cilium degeneration. Claudin-immunoreactivity was not evident in cilia of photoreceptor cells, epithelia of nasal mucosa, small intestine, or colon, suggesting that claudin may be a unique molecule in RPE cilia. These data suggest that cilia of the RPE, unlike cilia on other cell types, contain claudin, and that this molecule may play an important and specific role in the function and/or maintenance of RPE cilia.

Animals↗
PubMed2002

Evidence that light modulates protein nitration in rat retina.

As part of ongoing efforts to better understand the role of protein oxidative modifications in retinal pathology, protein nitration in retina has been compared between rats exposed to damaging light or maintained in the dark. In the course of the research, Western methodology for detecting nitrotyrosine-containing proteins has been improved by incorporating chemical reduction of nitrotyrosine to aminotyrosine, allowing specific and nonspecific nitrotyrosine immunoreactivity to be distinguished. A liquid chromatography MS/MS detection strategy was used that selects all possible nitrotyrosine peptides for MS/MS based on knowing the protein identity. Quantitative liquid chromatography MS/MS analyses with tetranitromethane-modified albumin demonstrated the approach capable of identifying sites of tyrosine nitration with detection limits of 4-33 fmol. Using two-dimensional gel electrophoresis, Western detection, and mass spectrometric analyses, several different nitrotyrosine-immunoreactive proteins were identified in light-exposed rat retina compared with those maintained in the dark. Immunocytochemical analyses of retina revealed that rats reared in darkness exhibited more nitrotyrosine immunoreactivity in the photoreceptor outer segments. After intense light exposure, immunoreactivity decreased in the outer segments and increased in the photoreceptor inner segments and retinal pigment epithelium. These results suggest that light modulates retinal protein nitration in vivo and that nitration may participate in the biochemical sequela leading to light-induced photoreceptor cell death. Furthermore, the identification of nitrotyrosine-containing proteins from rats maintained in the dark, under non-pathological conditions, provides the first evidence of a possible role for protein nitration in normal retinal physiology.

Albumins↗
PubMed2002

Spectral profiling of autofluorescence associated with lipofuscin, Bruch's Membrane, and sub-RPE deposits in normal and AMD eyes.

PURPOSE: To compare the autofluorescence spectra of retinal pigment epithelium (RPE)-associated lipofuscin, Bruch's membrane, and sub-RPE deposits (drusen and basal laminar-linear deposits) in eyes of donors with age-related macular degeneration (AMD) against eyes of age-matched control donors. METHODS: Cryosections were cut from the maculae of unfixed human donor eyes with AMD or from age-matched control eyes. Tissues were excited at wavelengths of 364, 488, 568, and 633 nm. Emission spectra were collected with a confocal microscope equipped with a spectrophotometric detector at 10-nm wavelength intervals between 400 and 800 nm. RESULTS: RPE lipofuscin had strong autofluorescent emissions that were excited at all wavelengths. Bruch's membrane exhibited strong autofluorescence with an emission peak of 485 +/- 5 nm when excited with 364-nm light. At 488-, 568-, and 633-nm excitations, Bruch's membrane and sub-RPE deposits in normal eyes exhibited minimal autofluorescence. In AMD eyes, however, both the 364- and 488-nm excitation wavelengths stimulated substantial blue-green emissions from sub-RPE deposits and Bruch's membrane, with average pixel intensities substantially exceeding that elicited in the yellow-orange range by RPE lipofuscin. CONCLUSIONS: These data suggest that an increase in blue-green autofluorescence of Bruch's membrane relative to the yellow-orange autofluorescence of RPE-associated lipofuscin is associated with AMD. Knowledge of these spectra will be useful in evaluating animal models of macular degenerative disease and in diagnosis of AMD, and will provide a novel signature for further analysis of the molecular entities emitting these fluorescent signatures.

Aged↗
PubMedDate not supplied

Transretinal electrical stimulation with a suprachoroidal multichannel electrode in rabbit eyes.

PURPOSE: Several approaches for placing an electrode device for visual prosthesis have been previously proposed. In this study, we investigated if transretinal stimulation from the suprachoroidal space can elicit an electrical evoked potential (EEP) in albino rabbits. METHODS: A flat electrode array (polyimide plate, platinum electrode) was developed and used for this study. After performing a scleral incision at 2-2.5 mm from the limbus and placing an anchoring suture, the array was inserted into the suprachoroidal space in the posterior portion of the eye by direct observation under a microscope. A platinum wire was implanted into the vitreous space as a reference electrode. For electrical stimulation, a biphasic pulse was used. When the electrode was stimulated, the EEP was recorded. RESULTS: When the electrical stimulation from the suprachoroidal space was applied, the EEP could be recorded with an epidural electrode, and the threshold was 66.0 +/- 32.1 micro A (420 micro C/cm(2)) [corrected]. placement of the array and the electrical stimulation. CONCLUSIONS: Transretinal electrical stimulation from the suprachoroidal space could elicit EEP, suggesting that this approach may be useful for a retinal prosthesis system.

Animals↗