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Oral hypofunction is the stage at which recovery can be expected with proper diagnosis, management, and motivation before oral dysfunction occurs. The knowledge and attitude toward oral function can influence the maintenance and improvement of oral function. However, whether middle-aged and older adults with declining oral function have knowledge of their oral function and how this knowledge and their attitude affect their oral function are unclear. Therefore, we aimed to examine (1) the relationship between knowledge and attitude toward oral function and hypofunction in individuals with suspected oral hypofunction and (2) changes in knowledge and attitude toward oral function through evaluation and education. Participants aged ≥50 years were enrolled during their first community dental clinic visit. A questionnaire assessment of knowledge and attitudes before and after oral function evaluation was performed. The oral function was initially assessed with seven criteria: oral hygiene; oral dryness; occlusal force; tongue pressure; tongue-lip motor, masticatory, and swallowing function. Associations between knowledge and attitudes and their changes were statistically analyzed. Fifty-nine participants (93.7%) were unaware of "oral hypofunction." Associations between knowledge and attitudes and their changes in the negative to positive response groups, from 86.4% and 61.0% to 6.8% and 25.4%, respectively, after oral function evaluation, indicated that participants understood their oral function and the need for training. Middle-aged and older individuals with poor knowledge and attitudes were more likely to have a worse oral function; however, their knowledge and attitudes toward oral function could be improved through oral function assessment and education. [ABSTRACT FROM AUTHOR]

Maintaining oral hygiene is an important yet often neglected aspect of rehabilitation medicine. Our visiting dental team, which provides dental treatments and swallowing rehabilitation, partnered with a medical hospital that had no dental department and began visiting and treating inpatients at this hospital. This study is aimed at evaluating the effects of dysphagia rehabilitation, and this was jointly conducted by medical and dental hospitals. The survey was conducted between May 2017 and March 2018. We retrospectively examined dysphagia rehabilitation provided to 25 patients (12 men and 13 women) aged 40–92 years (mean age: 77.1 ± 12.3 years). The largest number of requests for dental treatment was received from the internal medicine department (13 requests, 52.0%). A total of 39 videofluoroscopic or videoendoscopic examinations of swallowing interventions for dysphagia rehabilitation were conducted. All patients' oral and swallowing functions were evaluated using the functional oral intake scale (FOIS). At initial assessment, 9, 13, and 0 patients were at FOIS levels 1, 2, and 3 (use of tube feeding), respectively, and 1, 2, and 0 patients were at FOIS levels 4, 5, and 6 (only oral feeding), respectively. At the final assessment, 6, 10, and 4 patients were at FOIS levels 1, 2, and 3, respectively, and 0, 2, and 3 patients were at FOIS levels 4, 5, and 6, respectively. Oral and swallowing functions differed significantly between the first and final visits (p = 0.02). Visits conducted by a team of oral health practitioners to a medical hospital without a dental department appear to have a major impact and will become even more important in the future. [ABSTRACT FROM AUTHOR]

Background: During mastication, the tongue presses the bolus into the pharynx by a "squeeze‐back" motion, known as stage II transport (St2Tr). However, the pressure of St2Tr tongue‐palate contact has not been examined. Objectives: We aimed to clarify aspects of St2Tr occurrence and tongue‐palate contact during mastication by measuring tongue pressure. Methods: Ten healthy adults (eight men, two women, aged 26.8 ± 2.2 years) were enrolled. Tongue pressure was measured (Swallow Scan) during mastication. Sensors were placed on the palate near the incisive papilla (Ch.1), in the middle (Ch.2), at the posterior (Ch.3), and near the first molars on the habitual (Ch.H) and non‐habitual (Ch.Nh) masticatory sides. Nasopharyngeal endoscopy confirmed St2Tr and swallowing. Tongue pressures were measured repeatedly, from mastication onset through the first swallow, until eight sets of data were obtained. Tongue‐palate contact frequencies, integrated values of tongue pressure, and mastication times were recorded for St2Tr(+) and St2Tr(−) mastication conditions. Results: St2Tr occurred in 43 of 80 trials (53.8%). St2Tr(+) exhibited the highest tongue‐palate contact frequency at Ch.H; it exhibited higher contact frequencies at Ch.2, Ch.3 and Ch.H than St2Tr(−). St2Tr(+) exhibited higher tongue pressures at Ch.1, Ch.2 and Ch.H than at Ch.3; it exhibited higher tongue pressures at Ch.1 and Ch.2 than St2Tr(−). Conclusion: The study suggested that during St2Tr, the tongue frequently touched the palate at the central and posterior regions, as well as at its habitual masticatory side. It applies the strongest pressure at the anterior and central palate to transport the bolus to the pharynx. [ABSTRACT FROM AUTHOR]

Involved with various bodily functions, including ingestion and swallowing, the tongue is an important organ. We measured resting tongue hardness using real-time tissue elastography (RTE) to establish a simple tongue evaluation for patients who may have limited capacities to follow commands. Relationships between tongue hardness, thickness, and pressure were investigated, using both intra- and extraoral probes. Assessments were performed for a total of 27 healthy adults (11 male, 16 female, average age 26.4 ± 1.8 years). Measurements of tongue hardness and thickness were made using strain ratios (SR), and averaged across nine images. Maximum tongue pressure was determined using a tongue pressure device. A negative correlation was observed between intraorally measured tongue hardness and maximum tongue pressure (r = −0.76, p < 0.01). A positive correlation between extraorally measured tongue thickness and maximum tongue pressure was observed (r = 0.59, p < 0.01). Additionally, significant differences were observed between males and females with regards to intraorally measured tongue hardness (p = 0.02), maximum tongue pressure (p = 0.02), and extraorally measured tongue thickness (p < 0.01). The results of this study demonstrated the clinical applicability of RTE-based tongue hardness measurements, and suggest the feasibility of predicting tongue strength based on extraoral tongue thickness measurements. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the relationship between laser speckle flowgraphy (LSFG) and optical coherence tomography angiography (OCTA) measurements of the peripapillary retina and optic nerve head (ONH) in normal eyes and eyes with primary open-angle glaucoma (POAG). Patients and methods: One eye from each of 46 normal subjects and mild and moderate/advanced POAG patients were included. ONH blood flow acquired by LSFG, circumpapillary vessel density (cpVD, a 250 μm-wide elliptical annulus around the optic disc), and intra-papillary vessel density (ipVD, a 1.5×1.5 mm scan field) acquired by OCTA were measured. Their values were compared among normal controls and patients at each stage of glaucoma using one-way ANOVA, and the correlation between measurements obtained by the two methods was examined by univariate regression analysis. Results: ONH tissue blood flow, tissue mean blur rate (MBR-T), and cpVD in the outer layer of the retina significantly decreased with the progression of glaucoma stage, although the latter showed no significant difference between normal subjects and mild-stage glaucoma patients. MBR-T was significantly correlated with cpVD, but not with ipVD, in the retinal outer layer. Conclusion: A correlation was found only between MBR-T and cpVD in the retinal outer layer. A difference in MBR-T, but not in cpVD, was detected between normal controls and mild glaucoma patients. [ABSTRACT FROM AUTHOR]

Purpose. The present study aimed to examine changes in optic nerve head (ONH) blood flow autoregulation in 4 quadrants (superior, nasal, inferior, and temporal) with decreased ocular perfusion pressure (OPP) during vitrectomy in order to determine whether there is a significant difference of autoregulatory capacity in response to OPP decrease at each ONH quadrant. Methods. This study included 24 eyes with an epiretinal membrane or macular hole that underwent vitrectomy at Toho University Sakura Medical Center. Following vitrectomy, the tissue mean blur rate (MBR), which reflects ONH blood flow, was measured. Mean tissue MBRs in the four quadrants were generated automatically in the software analysis report. Measurements were conducted before and 5 and 10 min after intraocular pressure (IOP) elevation of approximately 15 mmHg in the subjects without systemic disorders. Results. The baseline tissue MBR of the temporal quadrant was significantly lower than that of the other 3 quadrants (all P<0.05). However, the time courses of tissue MBR in response to OPP decrease were not significantly different among the four quadrants during vitrectomy (P=0.23). Conclusions. There is no significant difference in the autoregulatory capacity of the four ONH quadrants in patients without systemic disorders during vitrectomy. [ABSTRACT FROM AUTHOR]

Purpose: To examine whether hypertension (HTN) and hyperlipidemia (HL) affect autoregulation of optic nerve head (ONH) blood flow during vitrectomy. Design: Cohort study. Methods: Seventeen eyes from 17 subjects with HTN and HL and 19 eyes from 19 control subjects without systemic disorders underwent vitrectomy for the treatment of epiretinal membrane or macular hole. Following standard 25-gauge microincision vitrectomy, the mean blur rate (MBR), which is an index of relative ONH blood flow, in the vascular area (vascular MBR) and MBR in the tissue area (tissue MBR) were measured using laser speckle flowgraphy. Measurements were conducted before and 5 and 10 min after an approximately 15-mmHg rise in intraocular pressure (IOP). Both parameters represent relative values of ONH blood flow (%, compared to baseline). The recovery rate of blood flow to the ONH was calculated using the following equation: (MBR at 10 min − MBR at 5 min)/(MBR at baseline − MBR at 5 min). Results: Ocular perfusion pressure in all subjects was reduced both 5 and 10 min after the increase in IOP. Vascular MBR in subjects with HTN and HL (75.5 ± 14.8) was significantly lower than that in control subjects (86.7 ± 12.1) 10 min after IOP elevation ( P = 0.019). The recovery rate of vascular blood flow was significantly lower in the HTN and HL groups than in the control group ( P = 0.002). Conclusions: Our results suggest that HTN and HL impair autoregulation in the vascular component of ONH blood flow during vitrectomy. [ABSTRACT FROM AUTHOR]

Aim Dysphagia is common in dependent older adults. Thus, a method of evaluating eating and swallowing functions that can be used to diagnose and manage dysphagia in a simple and robust manner is required. In 2002, the Mann Assessment of Swallowing Ability (MASA) was introduced to identify dysphagia in acute-stage stroke patients. As the MASA enables easy screening, it might also be applicable to dependent older adults if appropriate MASA cut-off values and the most useful assessment items could be determined. In the present study, we attempted to determine suitable MASA cut-off values, and the most useful assessment items for predicting aspiration and pharyngeal retention in dependent older adults. Methods Using the MASA, we evaluated the eating and swallowing functions of 50 dependent older adults with dysphagia. All of the patients also underwent videoendoscopic-based swallowing evaluations to detect aspiration and pharyngeal retention. The participants' characteristics and the utility of each assessment item were compared between various groups. Using the patients' videoendoscopic findings as a reference, receiver operating characteristic curve analysis was carried out to determine appropriate cut-off values for predicting aspiration and pharyngeal retention in dependent older adults. Results The optimal MASA cut-off values for predicting aspiration and pharyngeal retention were 122 points and 151 points, respectively. A total of 17 of the 24 clinical items assessed by the MASA were found to be associated with aspiration in dependent older adults. Conclusions The MASA is a useful screening tool for evaluating eating and swallowing functions in dependent older adults. Geriatr Gerontol Int 2017; 17: 561-567. [ABSTRACT FROM AUTHOR]

Purpose: To investigate optic nerve head (ONH) blood flow changes resulting from intraocular pressure (IOP) elevation in subjects without systemic disorders. Materials and Methods: Eighteen eyes of 18 patients who underwent vitrectomy to treat an epiretinal membrane or macular hole at Toho University Sakura Medical Center were included. Following standard 25-gauge microincision vitreous surgery, mean blur rate (MBR) in tissue (MT), an index of ONH blood flow, was measured using laser speckle flowgraphy. Measurements were taken before and 5 and 10 minutes after a 15 mmHg IOP elevation. Results: The ONH blood flow was initially lower than baseline (P= 0.001) after elevating IOP from 14.8 ± 2.8 mmHg to approximately 30 mmHg. Between 5 and 10 minutes after elevating IOP, ONH blood flow partially recovered (P= 0.004), even though ocular perfusion pressure was 20.2% lower than at baseline. Conclusions: The ONH blood flow in subjects without systemic disorders was initially lower, but began to recover 5–10 minutes after a 15 mmHg elevation in IOP. These results indicate that autoregulatory mechanisms of ONH blood flow may help to minimize the effects of IOP elevations and fluctuations during vitreous surgery. [ABSTRACT FROM PUBLISHER]

Propose: To evaluate relationships between optic nerve head (ONH) circulation by laser speckle flowgraphy (LSFG), and secretion levels of plasma norepinephrine (NE), plasma renin activity (PRA), plasma aldosterone concentration (PAC), and plasma cortisol. Method: Forty subjects were included in the study. The mean blur rates (MBR) throughout the ONH (MBR-all), in the tissue (MBR-tissue), and in vessels (MBR-vessel) were analyzed. In 29 subjects the following parameters were evaluated: plasma NE and ONH circulation in the evening and morning (Δ plasma NE, Δ MBR-all, -tissue, -vessel, and Δ area ratio of blood stream). Results: Plasma NE was significantly correlated with MBR-all ( r = 0.39, P = 0.01) and MBR-vessel ( r = 0.51, P = 0.0008). Plasma cortisol was significantly correlated with MBR-vessel ( r =0.35, P = 0.03). The PRA ( r = 0.31, P = 0.05) and PAC ( r = 0.31, P = 0.05) tended to correlate with MBR-vessel. The multiple regression analysis revealed that plasma NE, PAC, and ocular perfusion pressure (OPP) were identified as factors contributing independently to the MBR-vessel (plasma NE: standard regression = 0.48, t-value = 3.12, P = 0.004; PAC: 0.43, 3.10, 0.04; OPP: 0.58, 2.34, 0.03, r = 0.71). Positive correlations between Δ plasma NE and Δ MBR-all ( r = 0.46, P = 0.01), Δ MBR-tissue (0.38, 0.04), Δ MBR-vessel (0.41, 0.03), and Δ area ratio of blood stream (0.38, 0.04) were observed. Conclusion: Our results clarified that the measurements of ONH circulation by LSFG is reflecting the plasma secretion levels of vasoactive mediators. [ABSTRACT FROM AUTHOR]

Background: We encountered a rare patient with lens luxation in which the lens had become stuck on the optic disc. Findings obtained during vitreous surgery suggested that the luxated lens had become stuck on the optic disc via residual vitreous gel.Case Presentation: An 88-year-old Japanese man experienced lens luxation into the inferior vitreous cavity while undergoing treatment for glaucoma in his left eye. Because no inflammation was present upon examination, we observed the patient without prescribing any additional medications except for the eye drop treatment for glaucoma. Two years later, the patient revisited our clinic after suddenly noticing a visual disturbance in his left eye. A fundus examination revealed that the luxated lens had become stuck on the optic disc and displayed no changes in relation to the patient's head position or eye movement. Subsequently, vitreous surgery was performed to remove the luxated lens. During the surgery, we observed an aggregation of vitreous gel between the luxated lens and the optic disc. The luxated lens was successfully mobilized by pushing with a vitreous cutter and then extracted through a corneoscleral incision using perfluorocarbon liquid. At 4 months after surgery, the patient's visual acuity had improved to 20/25.Conclusions: The findings of this study suggest that the luxated lens had become stuck on the optic disc via residual vitreous gel on the optic disc. The surgical procedure of extracting the luxated lens through a corneoscleral incision using perfluorocarbon liquid was found to be both safe and effective. [ABSTRACT FROM AUTHOR]

Purpose: Müller cells are dedifferentiated after retinal injuries and are transformed into nestin-positive progenitor cells that play crucial roles in remodeling. The purpose of this study was to determine the changes in the expression of nestin, CD44 (a receptor of hyaluronan), vascular endothelial growth factor (VEGF), and glutamine sythetase in cultured Müller cells after dedifferentiation by basic fibroblast growth factor (bFGF) and insulin.Methods: Cells from a rat retinal Müller cell line (TR-MUL5) and from primary rat retinal Müller cells were grown in culture. The cells were incubated in various concentrations of bFGF (1.0, 10, 100 ng/mL) with or without insulin (5 μM) for 48 h. Changes in the expression of nestin, CD44, VEGF, and glutamine synthetase were determined by immunoblot and immunohistochemistry.Results: Exposure of TR-MUL5 cells to 10 ng/mL of bFGF led to the maximum increase in nestin by 1.5-fold, whereas the exposure had no effects on the expression of CD44. Addition of insulin (5 μM) to the bFGF significantly increased the CD44 level in TR-MUL5 cells by 1.4-fold. Immunohistochemistry showed that the combined treatments also upregulated the expression of nestin and CD44 in primary retinal Müller cells. Immunoblot analyses showed that exposure to bFGF and insulin caused significant increases of nestin (4.9-fold), CD44 (3.4-fold), and VEGF (1.44-fold) and decreases in glutamine synthetase (0.7-fold).Conclusions: The inflammation and angiogenesis that develop after retinal injuries may be due to an upregulation of CD44 and VEGF by the dedifferentiated Müller cells. [ABSTRACT FROM AUTHOR]

Autotaxin, also known as ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2), is a secreted enzyme that has lysophospholipase D activity, which converts lysophosphatidylcholine to bioactive lysophosphatidic acid. Lysophosphatidic acid activates at least six G-protein coupled recpetors, which promote cell proliferation, survival, migration and muscle contraction. These physiological effects become dysfunctional in the pathology of cancer, fibrosis, and pain. To date, several autotaxin/ENPP2 inhibitors have been reported; however, none were able to completely and continuously inhibit autotaxin/ENPP2 in vivo. In this study, we report the discovery of a highly potent autotaxin/ENPP2 inhibitor, ONO-8430506, which decreased plasma lysophosphatidic acid formation. The IC50 values of ONO-8540506 for lysophospholipase D activity were 6.4–19 nM for recombinant autotaxin/ENPP2 proteins and 4.7–11.6 nM for plasma from various animal species. Plasma lysophosphatidic acid formation during 1-h incubation was almost completely inhibited by the addition of >300 nM of the compound to human plasma. In addition, when administered orally to rats at a dose of 30 mg/kg, the compound demonstrated good pharmacokinetics in rats and persistently inhibited plasma lysophosphatidic acid formation even at 24 h after administration. Smooth muscle contraction is a known to be promoted by lysophosphatidic acid. In this study, we showed that dosing rats with ONO-8430506 decreased intraurethral pressure accompanied by urethral relaxation. These findings demonstrate the potential of this autotaxin/ENPP2 inhibitor for the treatment of various diseases caused by lysophosphatidic acid, including urethral obstructive disease such as benign prostatic hyperplasia. [ABSTRACT FROM AUTHOR]

With nitromethane and diphenylsilane (Ph2SiH2), zinc triflate behaves as a Lewis acid catalyst for the cyanation of nitrogen-containing heteroarenes such as indoles and pyrroles. This is the first realization of the Lewis acid-catalyzed direct cyanation of a C(aryl)H bond with no CN group-containing cyanating agent. [ABSTRACT FROM AUTHOR]

Neuroinflammation is involved in the death of retinal ganglion cells (RGCs) after optic nerve injury. The purpose of this study was to determine whether systemic simvastatin can suppress neuroinflammation in the optic nerve and rescue RGCs after the optic nerve is crushed. Simvastatin or its vehicle was given through an osmotic minipump beginning one week prior to the crushing. Immunohistochemistry and real-time PCR were used to determine the degree of neuroinflammation on day 3 after the crushing. The density of RGCs was determined in Tuj-1 stained retinal flat mounts on day 7. The effect of simvastain on the TNF-α-induced NF-κB activation was determined in cultured optic nerve astrocytes. On day 3, CD68-positive cells, most likely microglia/macrophages, were accumulated at the crushed site. Phosphorylated NF-κB was detected in some astrocytes at the border of the lesion where the immunoreactivity to MCP-1 was intensified. There was an increase in the mRNA levels of the CD68 (11.4-fold), MCP-1 (22.6-fold), ET-1 (2.3-fold), GFAP (1.6-fold), TNF-α (7.0-fold), and iNOS (14.8-fold) genes on day 3. Systemic simvastatin significantly reduced these changes. The mean ± SD number of RGCs was 1816.3±232.6/mm2 (n = 6) in the sham controls which was significantly reduced to 831.4±202.5/mm2 (n = 9) on day 7 after the optic nerve was crushed. This reduction was significantly suppressed to 1169.2±201.3/mm2 (P = 0.01, Scheffe; n = 9) after systemic simvastatin. Simvastatin (1.0 µM) significantly reduced the TNF-α-induced NF-κB activation in cultured optic nerve astrocytes. We conclude that systemic simvastatin can reduce the death of RGCs induced by crushing the optic nerve possibly by suppressing astroglial NF-κB activation. [ABSTRACT FROM AUTHOR]

Purpose: To report the short-term efficacy and safety of the transfer of an Ahmed™ glaucoma valve (AGV™) tube from the vitreous into the anterior chamber, in a patient with neovascular glaucoma who had undergone pars plana AGV™ implantation and ultimately needed a silicone oil tamponade. Case: A 41-year-old male with proliferative diabetic retinopathy in both eyes was referred to us for treatment in December 2009. Although the patient previously underwent several surgeries, he ultimately lost vision in his right eye. His left eye suffered from neovascular glaucoma after undergoing a pars plana vitrectomy for tractional retinal detachment. After several vitreous and glaucoma surgeries, the patient underwent implantation of a pars plana AGV™. Postoperatively, although his intraocular pressure was stabilized at approximately 10 mmHg, he had repeated vitreous hemorrhage and hyphema without improvement. He ultimately underwent PPV with a silicone oil tamponade and at the same time, the AGV™ tube was pulled out from the vitreous and inserted into the anterior chamber in order to avoid complications caused by the silicone oil. Results: At 19 months postoperative, the patient's intraocular pressure had stabilized at 10 mmHg with no recurrence of vitreous hemorrhage and hyphema. Eventually, he lost vision in his left eye because of cerebral hemorrhage. Conclusion: The findings show that insertion of a pars plana AGV™ tube into the anterior chamber in a patient undergoing a silicone oil tamponade is both effective and safe in the short-term. [ABSTRACT FROM AUTHOR]

Carbazole-type donor-π-acceptor (D-π-A) fluorescent dyes ( SO1 and SO2), each containing a diphenylamino system as an electron-donating group and a nitro moiety as an electron-accepting group, have been designed and synthesized, and their photophysical properties in solution and in the solid state have been investigated. The absorption and fluorescence properties of SO1 and SO2 in solution are similar, and both dyes exhibited moderate fluorescence quantum yields. In the solid state, however, the dye SO2, with a butyl substituent on the carbazole ring, exhibited red fluorescence at around 620 nm, whereas the dye SO1, with no substituent on the carbazole ring, did not exhibit these solid-state fluorescence properties. Furthermore, the dye SO2 exhibited weak mechanofluorochromic (MFC) properties: grinding of as-recrystallized dyes induces slight bathochromic shifts of the fluorescence excitation and emission maxima. To elucidate the effects of molecular and crystal structures on the solid-state fluorescence properties, we performed semiempirical molecular orbital calculations (PM3 and INDO/S) and single-crystal X-ray structural analysis. The X-ray crystal structures of SO1 and SO2 demonstrated that a continuous intermolecular π-stacking between the fluorophores was observable in the crystal structure of SO1, but not in that of SO2. The MO calculations revealed that SO1 and SO2 have similarly large dipole moments in the ground state ( μg ≈ 8 D). The relationship between the observed solid-state photophysical properties and the molecular and crystal structures of the carbazole-type D-π-A fluorescent dyes are discussed on the basis of experimental results and MO calculations. It is found that the formation of a continuous intermolecular π-stacking between the fluorophores causes a drastic fluorescence quenching in the solid state and that D-π-A fluorescent dyes with very large dipole moments can reduce the MFC properties, due to strong dipole-dipole interactions between the fluorophores in the solid state. [ABSTRACT FROM AUTHOR]

This study introduces a novel technique for estimating visual field by using overlapped fixation patterns obtained by the amounts of displacement in voluntary eye movements during searching-tracking trials, as an alternative screening medical device for visual field examination. The proposed system was evaluated by glaucoma patients in order to study whether or not the proposed system can be used as a visual field detection device for screening. The proposed system was found to detect visual field abnormality to a certain extent. However, there were some cases in which detection of Mariotte blind spots was inaccurately performed. The experimental results revealed that there was room to reconsider our understanding regarding the effect of ptosis, overlapping with eyesight, as well as calibration of the display position to the correct location to be examined. The results of the evaluation experiment indicated that this proposed system has the potential to be used as a visual field examination device for screening. © 2012 Wiley Periodicals, Inc. Electron Comm Jpn, 95(7): 29-40, 2012; Published online in Wiley Online Library (). DOI 10.1002/ecj.11384 [ABSTRACT FROM AUTHOR]

Modulation of enzyme activity through nitrosylation has recently been identified as a new physiological activity of nitric oxide (NO). We hypothesized that NO enhances the TNF-α-induced death of retinal neurons through a suppression of nuclear factor-κB (NF-κB) by nitrosylation. In this study, cells from the RGC-5 line were exposed to different concentrations (2.0, 10, and 50 ng/ml) of TNF-α, and the degree of TNF-α-induced cell death was determined by the WST-8 assay and by flow cytometric measurements of the externalization of phosphatidylserine. The effects of etanercept, a soluble TNFR-Fc fusion protein, and S-nitroso- N-penicillamine (SNAP), an NO donor, on the toxicity were determined. Experiments were also performed to determine whether nitric oxide synthase (NOS) was associated with the toxicity of TNF-α. The activation of NF-κB was determined by the detection of the p65 subunit in the nuclear extracts. Our results showed that exposure of RGC-5 cells to different concentrations of TNF-α significantly decreased the number of living cells in a dose-dependent way. The death was partially due to apoptosis with an externalization of phosphatidylserine, and the death was suppressed by etanercept. Exposure to TNF-α increased the activation of NF-κB and the expression of iNOS. Although NF-κB inhibitors suppressed the increase of iNOS, they also potentiated the TNF-α-induced death. Both L-NAME and aminoguanidine, both NOS inhibitors, rescued the cells from death. In contrast, addition of SNAP caused nitrosylation of the inhibitory κB kinase, and suppressed the NF-κB activation and potentiated the TNF-α-induced neurotoxicity. These results indicate that NO potentiates the neurotoxicity of TNF-α by suppressing NF-κB. [ABSTRACT FROM AUTHOR]

We observed surfaces and cross sections of thin hydroxyapatite (HA)-coated implants produced by the thermal decomposition method in a patient attending our clinic who underwent implant removal at 80 months due to fracture of the implants. On the implant surfaces of the removed sample, most of the HA had dissolved, and extensive osseointegration was observed where Ti had closely bonded to bone. This indicated that the HA coated on the implant surfaces had disappeared and osseointegration had been established where Ti directly bonded to the bone. In addition, calcium titanate (CaTiO3) and HA layers formed by the thermal decomposition method showed no desorption. The results clearly indicate the positive clinical potential of thin HA-coating by the thermal decomposition method. [ABSTRACT FROM AUTHOR]

Laser speckle flowgraphy (LSFG) allows for the quantitative estimation of blood flow in the optic nerve head, choroid, retina and iris in vivo. It was developed to facilitate the non-contact analysis of ocular blood flow in living eyes, utilizing the laser speckle phenomenon. The technique uses a fundus camera, a diode laser, an image sensor, an infrared charge-coupled device (CCD) camera and a high-resolution digital CCD camera. Normalized blur (NB), an approximate reciprocal of speckle contrast, represents an index of blood velocity, and shows a good correlation with tissue blood flow rates determined with the microsphere method in the retina, choroid or iris, as well as blood flow rates determined with the hydrogen gas clearance method in the optic nerve head. The square blur ratio (SBR), another index for quantitative estimation of blood velocity, is proportional to the square of the NB. The SBR is theoretically a more exact measurement which is proportional to velocity, whereas the NB is an approximation. Normalized blur was calculated in earlier versions of LSFG because of technical limitations; the SBR is used in current versions of the LSFG instrument. As these values are in arbitrary units, they should not be used to make comparisons between different eyes or different sites in an eye. Clinical protocols, calibration, evaluation procedures and possible limitations of the LSFG technique are described and the results of ocular blood flow studies using LSFG are briefly summarized. The LSFG method is suitable for monitoring the time-course of change in the tissue circulation at the same site in the same eye at various intervals, ranging from seconds to months. Unresolved issues concern the effect of pupil size on measurement results, the effects of various stimulations, and how to measure choroidal and retinal blood flow velocity separately without using the blue-component of argon laser. [ABSTRACT FROM AUTHOR]

Anaphylaxis is a life-threatening immediate hypersensitivity reaction triggered by antigen capture by immunoglobulin E (IgE) bound to the high-affinity IgE receptor (FcɛRI) on mast cells. However, the regulatory mechanism of mast cell activation is not completely understood. Here we identify an immunoglobulin-like receptor, Allergin-1, that contains an immunoreceptor tyrosine-based inhibitory motif (ITIM)-like domain, and show it was preferentially expressed on mast cells. Mouse Allergin-1 recruited the tyrosine phosphatases SHP-1 and SHP-2 and the inositol phosphatase SHIP. Coligation of Allergin-1 and FcɛRI suppressed IgE-mediated degranulation of bone marrow–derived cultured mast cells. Moreover, mice deficient in Allergin-1 developed enhanced passive systemic and cutaneous anaphylaxis. Thus, Allergin-1 suppresses IgE-mediated, mast cell–dependent anaphylaxis in mice. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of donepezil hydrochloride, an agent for the treatment of Alzheimer’s disease (AD), on the cerebral and optic nerve head (ONH) blood flow, visual field defect in normal-tension glaucoma (NTG) patients with decreased cerebral blood flow (CBF) that demonstrates an AD-like perfusion pattern. Methods: The subjects were 5 NTG patients who exhibited AD-like decreased CBF upon 123I-iodoamphetamine single photon emission computed tomography (123I-IMP SPECT). Donepezil hydrochloride (5 mg/day) was prescribed for each patient during a period of 12 months. Intraocular pressure (IOP), mean deviation (MD) of the Humphrey visual field, ONH blood flow determined by a laser speckle flowgraphy, and regional CBF (rCBF) determined by 123I-IMP SPECT were measured before and every 6 months during the treatment. Results: MD, ONH blood flow, and rCBF were improved significantly after 6 months of the treatment, although IOP did not change significantly. No deterioration of NTG morbidity was found in any of the measured parameters after 12 months of the treatment. Conclusions: Oral administration of donepezil hydrochloride in NTG patients might prevent deterioration of visual field defect, ONH blood flow, and rCBF in the temporal, parietal, and posterior lobes. This pilot study suggested the possibility that donepezil hydrochloride might ameliorate glaucomatous optic neuropathy in NTG. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine whether the brushing durability of a titanium dioxide coating on a polymethyl methacrylate (PMMA) substrate was improved by prior treatment with an acryloxypropyl trimethoxysilane-based agent. Titanium dioxide coatings were obtained by spray-coating substrates with or without prior treatment. Structure was investigated using IR, SEM, and an EPMA. Effect on durability against brushing was determined with a brush-wear test machine utilizing a commercial denture brush. A thin layer comprised of siloxane and TiO2 was formed on a PMMA substrate by prior treatment with an acryloxypropyl trimethoxysilane-based agent and spray-coating of TiO2. Prior treatment demonstrated improved stability against brushing, whereas the titanium coating was removed after less than 1x105 brushing cycles without prior treatment. This suggests that prior treatment with an acryloxypropyl trimethoxysilane-based agent would confer improved durability against brushing-induced stress on a TiO2 coating in its application to dentures. [ABSTRACT FROM AUTHOR]

Purpose To assess the effects of combined therapy with latanoprost and beta blockers on optic nerve head (ONH) blood flow in normal-tension glaucoma (NTG) patients. Methods Intraocular pressure (IOP), ONH blood flow (laser speckle flowgraphy) and blood pressure were measured in 15 eyes of 15 NTG patients (41–76 years old) before treatment or after a 1-month washout period. Similar measurements were performed at 2 months after the commencement of treatment with latanoprost and at 3 months after the start of combined therapy of latanoprost with 0.5% timolol or 2% carteolol in a crossover study using the envelope method. Measurement was carried out 2–3 hr after the morning application of eyedrops. Results Latanoprost decreased IOP with no significant change in ONH blood flow. Concomitant use of timolol or carteolol further decreased IOP with no significant difference between these two drugs. Only the combined therapy of latanoprost with carteolol significantly (p < 0.01) increased ONH blood flow by approximately 10%, compared to initial levels. There was no significant change in mean blood pressure, ocular perfusion pressure or pulse rate as a result of these therapies. Conclusion: Topical latanoprost–carteolol combined therapy increased ONH blood flow in NTG patients, unlike latanoprost–timolol therapy. Because ocular perfusion pressure was unchanged, direct vasodilative effects were suspected as the mechanism. [ABSTRACT FROM AUTHOR]

EAU in mice is a model of human posterior uveitis. EAU is a Th1-dependent disease that has been assumed to target the neural retina and related tissues; however, in situ effector cells and the target have not yet been clearly demonstrated. In the present study, we induced EAU in B10R mice by immunizing them with human interphotoreceptor retinoid-binding protein peptide 161–180. Histological examinations revealed that EAU occurred approximately 11 days after the immunization and reached a peak on day 14. Retinae from normal or EAU mice were treated with proteases to obtain mono-dispersed cells. The mono-dispersed cells thus obtained were separated into three to four fractions by discontinuous Percoll density-gradient (e.g. PBS/40/60) centrifugation. In normal mice, 94% of the total cells were recovered in two fractions (i.e. PBS/40 and pellet); and these fractions mainly contained inner and outer segments and cell bodies of photoreceptor cells and RPE cells, respectively. In EAU mice, additional cells (i.e. inflammatory cells) were obtained at the 40/60 interface. Electron microscopic examination showed that tissue damage during EAU was initiated by non-phagocytic destruction of inner segments by Mac-1+ mononuclear cells on day 11, followed by phagocytic activity of macrophages against outer segments and RPE cells on day 14. In vitro culturing of normal retinal cells with EAU infiltrates suggested the involvement of TNF-α and NO in the tissue damage. These results indicate that EAU was initiated by non-phagocytic destruction of inner segments of photoreceptor cells by Mac-1+ mononuclear cells. [ABSTRACT FROM AUTHOR]

Here, we examined whether amyloid-β (Aβ) protein participates in cell death and retinal function using three types of transgenic (Tg) mice in vivo [human mutant amyloid precursor protein (APP) Tg (Tg 2576) mice, mutant presenilin-1 (PS-1) knock-in mice, and APP/PS-1 double Tg mice]. ELISA revealed that the insoluble form of Aβ1-40 was markedly accumulated in the retinas of APP and APP/PS-1, but not PS-1 Tg, mice (vs. wild-type mice). In APP Tg and APP/PS-1 Tg mice, immunostaining revealed accumulations of intracellular Aβ1–42 in retinal ganglion cells and in the inner and outer nuclear layers. APP Tg and APP/PS-1 Tg, but not PS-1 Tg, mice had less NMDA-induced retinal damage than wild-type mice, and the reduced damage in APP/PS-1 Tg mice was diminished by the pre-treatment of N-[ N-(3,5-difluorophenacetyl)-l-alanyl]- S-phenylglycine t-butyl ester, a γ-secretase inhibitor. Furthermore, the number of TUNEL-positive cells was significantly less in ganglion cell layer of APP/PS-1 Tg mice than PS-1 Tg mice 24 h after NMDA injection. The phosphorylated form of calcium/calmodulin-dependent protein kinase IIα (CaMKIIα), but not total CaMKIIα or total NMDA receptor 1 (NR1) subunit, in total retinal extracts was decreased in non-treated retinas of APP/PS-1 Tg mice (vs. wild-type mice). CaMKIIα and NR2B proteins, but not NR1, in retinal membrane fraction were significantly decreased in APP/PS-1 Tg mice as compared with wild-type mice. The NMDA-induced increase in p-CaMKIIα in the retina was also lower in APP/PS-1 Tg mice than in wild-type mice. In electroretinogram and visual-evoked potential recordings, the implicit time to each peak from a light stimulus was prolonged in APP/PS-1 mice versus wild-type mice. Hence, Aβ may impair retinal function by reducing activation of NMDA-receptor signaling pathways. [ABSTRACT FROM AUTHOR]

Purpose: To clarify the involvement of angiotensin II-dependent vascular endothelial growth factor (VEGF) via NADPH oxidase in the retina in spontaneously diabetic Torii (SDT) rats, a type 2 diabetic rat model. In SDT rats, the plasma glucose level and angiotensin-converting enzyme (ACE) levels were measured, and effects of angiotensin II receptor blocker (ARB) and angiotensin II were also studied. Materials and Methods: We evaluated the age-dependent changes in the peripheral and ocular angiotensin II-forming systems in SDT rats at 15 (n = 8), 20 (n = 8), 30 (n = 7), and 50 weeks of age (n = 8). We also evaluated the effect of an ARB (2.5 mg/kg/day candesartan) or angiotensin II (500 ng/kg/min) on retinal gene expressions of VEGF and p22phox, a subunit of NADPH oxidase. Results: The plasma glucose level was significantly increased from 20 weeks of age. No significant changes in ACE activities in the plasma, aorta, and eye were observed until 30 weeks of age. At 50 weeks, ACE activity in the eyes was significantly increased, whereas ACE activities in the plasma and aorta were not. At 50 weeks, significant increases in VEGF and p22phox, an NADPH oxidase subunit, were significantly reduced by candesartan. Angiotensin II infusion resulted in significant increases in VEGF and p22phox levels. Conclusions: Angiotensin II is involved in the gene expression of VEGF via NADPH oxidase in the retina of SDT rats. [ABSTRACT FROM AUTHOR]

Purpose: To determine the alterations in the expression of endothelin-1 (ET-1) and its specific receptors in the sensory retina after optic nerve injury. Methods: The optic nerve of the right eye of Wistar rats was crushed. The sensory retinas were removed 1, 2, 4, 7, and 14 days after the surgery, and the amount of ET-1 in the retinas was measured by radioimmunoassay, and the mRNA levels of ETA and ETB receptors were determined by real-time PCR. Results: The ET-1 levels in the sensory retinas following the optic nerve crush were 8.83 ± 2.23 and 9.99 ± 4.83 pg/mg protein on days 7 and 14 after the injury, while those in the sham controls were 4.55 ± 1.36 and 4.85 ± 1.57 pg/mg protein, respectively. The increase was significant on day 7 (p = 0.003, ANOVA followed by t- test), but not on day 14 (p = 0.054). The mRNA levels of the ETA and ETB receptors in the retina after the optic nerve crush was significantly increased on day 7. A two-fold increase was recognized in ETB receptors. Immunohistochemical analyses revealed that the ET-1 expression was increased mainly in the inner retinal layers, including the nerve fiber layer and ganglion cell layer (GCL). The increased immunoreactivity of the ETB receptor was seen in the GCL cells and also in the outer nuclear layer. Conclusion: An increase in the intraretinal ET-1 may be involved in the retinal remodeling after the optic nerve is crushed. [ABSTRACT FROM AUTHOR]

The purpose if this study was to elucidate how extracellular ATP causes cell death in the retinal microvasculature. Although ATP appears to serve as a vasoactive signal acting via P2X7 and P2Y4 purinoceptors, this nucleotide can kill microvascular cells of the retina. Because P2X7 receptor activation causes transmembrane pores to form and microvascular cells to die, we initially surmised that pore formation accounted for ATP's lethality. To test this hypothesis, we isolated pericyte-containing microvessels from rat retinas, assessed cell viability using Trypan blue dye exclusion, detected pores by determining the uptake of the fluorescent dye YO-PRO-1, measured intracellular Ca2+ with the use of fura-2, and monitored ionic currents via perforated patch pipettes. As predicted, ATP-induced cell death required P2X7 receptor activation. However, we found that pore formation was minimal because ATP's activation of P2Y4 receptors prevented P2X7 pores from forming. Rather than opening lethal pores, ATP kills via a mechanism involving voltage-dependent Ca2+ channels (VDCC). Our experiments suggest that when high concentrations of ATP caused nearly all microvascular P2X7 receptor channels to open, the resulting profound depolarization opened VDCC. Consistent with lethal Ca2+ influx via VDCC. ATP-induced cell death was markedly diminished by the VDCC blocker nifedipine or a nitric oxide (NO) donor that inhibited microvascular VDCC. We propose that purinergic vasotoxicity is normally prevented in the retina by NO-mediated inhibition of VDCC and P2Y4-mediated inhibition of P2X7 pore formation. Conversely, dysfunction of these protective mechanisms may be a previously unrecognized cause of cell death within the retinal microvasculature. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effects of bunazosin hydrochloride, an α 1 -adrenergic blocker, on the impairment of optic nerve head (ONH) blood flow and depression of visual function induced by repeated intravitreal injections of endothelin-1 (ET-1) in rabbits. Method: We injected ET-1 (20 pmol) into the right posterior vitreous of rabbits twice a week for 4 weeks, and the observation period was set at 8 weeks (starting from the first injection). The animals that received ET-1 were divided into two groups: twice a day for 8 weeks, one group received topical 0.01% bunazosin, while the second received the vehicle for bunazosin. The ONH blood flow was monitored using the laser speckle method, and visual function was assessed by examining visually evoked potentials (VEPs). Changes in the ONH cup/disk area and in the number of cells in the retinal ganglion cell layer (GCL) were also determined.Results: Repeated injections of ET-1 decreased the ONH blood flow, prolonged the VEP implicit time, enlarged the optic cup, and decreased the number of GCL cells. Topical bunazosin significantly decreased these impairments. Conclusions: These results indicate that in rabbits, topical bunazosin suppresses the changes in ONH circulation and function induced by intravitreal ET-1. [ABSTRACT FROM AUTHOR]

Purpose. To determine whether adenosine can protect cultured retinal neurons, consisting mainly of amacrine cells. from N-methyl-D-aspartate (NMDA)-induced neurotoxicity, and to determine whether agonists and antagonists of adenosine receptors also have a protective effect. Methods. Cultured retinal neurons obtained from fetal Wistar rats (gestational age 18-19 days) were maintained for 10-11 days. Neurons were exposed to NMDA (1.0 mM) for 10 min with or without adenosine or to NMDA with adenosine receptor agonists or antagonists. Neuronal death was assessed by the trypan-blue exclusion method 24 hr alter the exposure. Results. Adenosine at doses of 0.01 μM and higher significantly protected (p < 0.05, Dunnett) primary cultured fetal rat retinal neurons from apoptotic and/or necrotic death induced by NMDA (1.0 μM). The protective effect of adenosine (10 μM) against NMDA-induced neuronal death was lost by simultaneous exposure to selective A1 receptor antagonist but not to A2a receptor antagonist. Selective A1 receptor agonists had similar effects as adenosine, but A2a receptor agonists and 8-Br-cyclic AMP bad no effect on cell viability. Conclusions. Adenosine can protect cultured retinal neurons against NMDA-induced cell death via the A1 receptor. [ABSTRACT FROM AUTHOR]

Purpose. Excessive activation of poly(ADP-ribose) polymerase (PARP). a nuclear enzyme that is activated by DNA damage, leads to neuronal cell death through depletion of ATP The purpose of this study was to determine whether inhibition of PARP has some neuroprotective effects on the N-methyl- D-aspartate (NMDA)-induced functional and morphological injury to the rabbit retina. Methods. Visually evoked potentials (VEPs) were recorded at different times after an intravitreal injection of NMDA (200. 660. and 2000 nmol) alone, or NMDA with 3- aminobenzamide (ABA. 200 nmol). a PARP inhibitor, or with MK-801 (200 nmol), an NMDA antagonist. The physiological changes were followed for 2 weeks, after which the eyes were enuculeated and prepared for histological examinations. Results. Intravitreal injections of NMDA reduced the amplitudes of rabbit VEPs and the number of cells in the retinal ganglion cell layer in a dose-dependent manner. No significant changes could be detected in the bright-flash electroretinograms (ERGs). Simultaneous injection of MK-801 (200 nmol) significantly diminished the changes induced by intravitreal NMDA. 3-Aminoben7amide (ABA) (200 nmol) also suppressed these changes, but its effects were less than those of MK-801 Conclusions. NMDA-induced retinal damage can be detected by VEPs, and PARP inhibition has some neuroprotective effects on the NMDA-induced retinal damage. [ABSTRACT FROM AUTHOR]

We evaluated changes in ocular hemodynamics induced by nipradilol, an NO donor, applied as an eye drop. Eight volunteers underwent color Doppler imaging for measurement of hemodynamic parameters in the central retinal artery (CRA) and ophthalmic artery (OA) after instillation of nipradilol. Intraocular pressure (IOP) and systemic blood pressure were also measured. Two months later, the same volunteers were examined after instillation of saline into the same eyes to obtain control data. The pulsatility index in the CRA was significantly lowered in the eyes treated with nipradilol compared with control eyes. Blood velocities in the CRA, hemodynamic parameters in the OA, IOP, blood pressure, and ocular perfusion pressure were unaffected by nipradilol. The current study suggests that nipradilol may dilate the CRA as a result of reduced vascular resistance in humans. [ABSTRACT FROM AUTHOR]

We investigated whether topical instillation of an α[sub 1]-adrenergic blocker would improve an insufficient blood supply in the optic nerve head (ONH) and visual function, in rabbits. The effect of systemic NOS inhibition on visual-evoked potentials (VEPs) and hemodynamics in ONH were determined. VEPs were recorded before and every 15 min during a 120-min observation period after an intravenous injection of 50 mg/kg N[sup G]-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor. Capillary blood flow in ONH was evaluated by the laser speckle method throughout the same period. Then, we investigated the effect of topical instillation of a recently developed α[sub 1] adrenergic blocker, bunazosin hydrochloride (0.01%), 60 min prior to the intravenous L-NAME (50 mg/kg) on the changes by NOS inhibition. The VEP amplitudes were reduced by L-NAME (10, 20, and 50 mg/kg) in a dose-dependent manner, while the VEP implicit time was unchanged, and no significant changes were detected in the electroretinogram. The reductions in ONH capillary blood flow and VEP amplitudes caused by L-NAME (50 mg/kg) were significantly suppressed by an instillation of bunazosin hydrochloride. These results indicate that blocking α[sub 1]-adrenergic receptors may ameliorate the impairments in blood flow and retinal function caused by NOS inhibition. The enhancement of basal vascular tone due to deprivation of continuous NO production may be diminished by this α[sub 1]-adrenergic blocker. [ABSTRACT FROM AUTHOR]

Purpose. To investigate the changes in retinal blood flow (RBF) during a 75-g oral glucose tolerance test in the contralateral eye of patients with retinal branch vein occlusion (BRVO). Methods. Seventeen patients with BRVO were included. None had a known history of diabetes mellitus. The blood velocity and vessel diameter of the upper temporal retinal artery in the contralateral eye were measured using laser Doppler velocimetry with an eye-tracking system before and 1, 2, and 3 h after oral intake of 75 g glucose. Blood sugar, systemic blood pressure, and intraocular pressure were monitored. Eleven healthy volunteers were examined similarly as control. Results. Nine patients (53%) with BRVO had an abnormal pattern on the glucose tolerance test. RBF significantly increased at 1, 2, and 3 h in eight patients with normal glucose tolerance. The changes in RBF primarily resulted from changes in vessel diameter; the blood velocity did not change significantly. The nine patients with impaired glucose tolerance or diabetes mellitus had a RBF pattern that was significantly lower at 2 and 3 h than those with normal oral glucose tolerance. In the control group, all 11 volunteers showed the same increases in RBF at 2 and 3 h as the BRVO patients with a normal glucose pattern. Conclusion. A relatively high number of patients with BRVO had an abnormal pattern on glucose tolerance testing. Glucose intake increased RBF in BRVO patients without diabetes and in healthy volunteers. The RBF response may differ between subjects with diabetes and those without diabetes. [ABSTRACT FROM AUTHOR]

Purpose. Two pathways for the formation of angiotensin II (Ang II) in local tissues are known to exist, one involving angiotensin-converting enzyme (ACE), and the other in which chymase plays a role. It has been shown that chymase activity is present in monkey, dog, and hamster eyes. Because chymase activates various cytokines by increasing Ang II formation, thereby promoting the production of extracellular matrix, the role of Ang II in wound healing has attracted much interest. In this work, we created sclerocorneal wounds in hamster eyes and measured the levels of ACE and chymase activities in the eye during the wound healing process. Methods. Sclerocorneal wounds were made at 6 locations on the corneal limbus of one eye in each of 36 hamsters. Using the contralateral eyes as controls, we measured levels of chymase and ACE activities in the overall eye at 3, 7, and 21 days postoperatively. Histopathological evaluations of the sclerocorneal wounds in the treated eyes were also carried out for samples stained with toluidine blue. Results. Chymase activity in the treated eyes tended to be higher than that in the control at 21 days. ACE activity in the treated eyes was significantly higher than that in the control at 3, 7, and 21 days postoperatively. Histopathological examination revealed increased mast cells in the subconjunctival tissue and around the tunnel opening in the sclerocornea. Conclusions. These findings show that not only ACE but also chymase contributes to the formation of Ang II in the healing of sclerocorneal wounds in hamster eyes. This leads to the suggestion that ACE inhibitors or chymase inhibitors could potentially inhibit scarring in glaucoma filtering surgery. [ABSTRACT FROM AUTHOR]

Purpose. To evaluate the role of nitric oxide (NO) in the mechanism of the ocular hypotensive action of nipradilol, a β-blocker with α[sub 1]-blocking activity. Methods. Change in intraocular pressure (IOP) of albino rabbits was measured after a single application of carboxyPTIO (c-PTIO), an NO trapping agent. Next, IOP change was measured every hour for 5 hours after the instillation of 0.25% nipradilol into one of the eyes with and without cPTIO pretreatment of both eyes. IOP change induced by desnitro-nipradilol was also examined. The outflow facility and uveoscleral outflow were determined by two-level constant pressure and anterior chamber perfusion methods before and at 3 hours after the application of nipradilol with and without c-PTIO pretreatment. Results. Topical administration of c-PTIO showed no significant effect on IOP. Unilateral instillation of nipradilol reduced IOP significantly compared with control eyes with a maximum reduction of 3.6 mmHg and effect duration of 3 hours. Pretreatment with c-PTIO partially inhibited the reduction during an earlier period (1∼2 hours) and completely at 3 hours. IOP change by desnitro-nipradilol was similar to that by nipradilol with c-PTIO pretreatment. Nipradilol increased both outflow facility and uveoscleral outflow at 3 hours, whereas pretreatment with c-PTIO inhibited both of these outflows. Conclusions. Results indicate that ocular hypotensive action by nipradilol during the relatively late period may be mainly due to enhancement of aqueous humor outflow by NO at least in the rabbits. [ABSTRACT FROM AUTHOR]

Purpose. To study the effects of topically applied nipradilol, an α-B blocker recently developed in Japan as an ocular hypotensive drug, on retinal blood flow (RBF) in healthy volunteers. Methods. Seven healthy volunteers (mean age, 33 years) underwent measurement of RBF using a newly developed stabilized laser Doppler velocimetry system. In a double-blind trial, retinal arterial blood flow, intraocular pressure (IOP), and blood pressure (BP) were measured before and after the instillation of nipradilol or saline every hour for 5 hours. Results. Retinal arterial blood flow and the diameter of the retinal artery significantly (p < 0.05) increased at 4 hours after installation in nipradilol-treated eyes. Retinal blood velocity did not change in significantly. Nipradilol evoked a significant (p < 0.05) bilateral decrease in IOP. Mean BP decreased significantly (p < 0.05) 3 hours after installation. Ocular perfusion pressure (OPP), calculated from the mean BP and IOP, did not change significantly during the study. Conclusion. Topical nipradilol significantly increased retinal arterial blood flow in healthy volunteers, not through a secondary effect dependent on a change in OPP, but likely through the vasodilatory action of the drug. [ABSTRACT FROM AUTHOR]

We examined the effects of lomerizine, a new diphenylmethylpiperazine Ca[sup 2+] channel blocker, on the normal circulation in the optic nerve head and long posterior ciliary artery, and on endothelin-1-induced hypoperfusion in the optic nerve head in anesthetized rabbits using a hydrogen gas clearance method and laser Doppler flowmetry. These effects were compared with those of nilvadipine and pranidipine. Lomerizine (0.1 and 0.3 mg/kg, i.v.) significantly increased tissue blood flow in the optic nerve head and the putative blood flow in the long posterior ciliary artery with smaller reduction of blood pressure (0.3 mg/kg, i.v.) and without change in heart rate. On the other hand, nilvadipine (0.003 and 0.01 mg/kg, i.v.) and pranidipine (0.003 and 0.01 mg/kg, iv.) each significantly increased blood flow and lowered blood pressure. Moreover, lomerizine (0.1 and 0.3 mg/kg, i.v.) and nilvadipine (0.01 mg/kg, i.v.), when administered 5 min before an endothelin-1 injection (10[sup -6] M, 100 μl), inhibited the hypoperfusion in the optic nerve head. These results suggest that lomerizine improves the ocular circulation with minimal cardiovascular side effects. Therefore, lomerizine may have clinical potential for the treatment of eye diseases associated with local circulatory disturbances, such as normal-tension glaucoma. [ABSTRACT FROM AUTHOR]

Purpose. To assess the influence of the blood glucose level on ocular capillary circulation, we induced clinically significant hyperglycemia (200-300mg/dl) in rabbits and investigated the changes in the optic nerve head (ONH) circulation. Methods. Hyperglycemia was induced by injection of glucose (5.6mmol/kg) into an auricular vein of healthy albino rabbits and changes in the ONH circulation were measured by the laser speckle method. In order to examine the role of nitric oxide (NO), glucose was administered after intravenous injection of an NO synthetase inhibitor (N[sup G]nitro-L-arginine methyl ester, L-NAME, l mg/kg), then changes in the ONH circulation were measured. Results. The blood glucose level reached a peak at 30 min after glucose loading and returned to its initial level by 2 hours. ONH circulation showed a 60% increase compared with its initial level at 15 min after glucose loading and subsequently remained almost unchanged throughout the 2-hour observation period. There were no significant changes of the blood pressure, heart rate, or intraocular pressure. The glucose-induced increase of ONH circulation was completely inhibited by pretreatment with L-NAME. Conclusions. ONH circulation was increased by administration of glucose to healthy rabbits. A high blood glucose level seems to promote ocular capillary circulation and NO as well as insulin appear to have a role in this process. [ABSTRACT FROM AUTHOR]

PURPOSE. To investigate the effect of topical iganidipine,a new dihydropyridine derivative calcium channel blocker, on impairment ofthe ocular circulation caused by endothelin-1 (ET-1), we examined modificationof the effect of ET-1 on visual-evoked potential (VEP) in albino rabbits. METHODS. To clarify whether VEP could be used to indicate the extent ofocular circulatory impairment, we evaluated the dose dependency of changesin VEP over 2 hours after intravitreal injection of 3 ET-1 doses (1.0, 3.3,or 10 pmol) and the vehicle. Then modification of the effect of ET-1 on theVEP by iganidipine was examined. One hour after the topical instillation of0.1% iganidipine (20 μl) or its vehicle, 10 pmol of ET-1 was injected intothe vitreous in rabbits. The VEP was measured for 2 hours after ET-1 application,and the response was compared between the eyes with iganidipine and vehiclepretreatment. RESULTS. Intravitreal injection of ET-1 dose-dependently reduced the VEPamplitude. Topical administration of 0.1% iganidipine significantly suppressedthe reduction of VEP amplitude for the entire 2-hour monitoring period afterintravitreal injection of 10 pmol ET-1. There was no significant change ofthe systemic blood pressure as well as intraocular pressure after topicaladministration of iganidipine. CONCLUSIONS. Iganidipine eyedrops may be useful for the treatment of ischemicretinal and optic nerve disorders related to abnormal ET-1 production forthe maintenance of visual function. [ABSTRACT FROM AUTHOR]