Biomedical subjects

Kenji Kashiwagi

Publications and source records attributed to Kenji Kashiwagi.

At least 19 recordsLinked to original sources

PubMed2006

Comparison of the scanning peripheral anterior chamber depth analyzer and the modified van Herick grading system in the assessment of angle closure.

PURPOSE: To compare the performance of the scanning peripheral anterior chamber depth analyzer (SPAC) and the modified van Herick grading system in the assessment of angle closure, using gonioscopy as the reference standard. DESIGN: Prospective comparative study. PARTICIPANTS: One hundred twenty phakic subjects (53 with primary angle closure and 67 with open angles) with no history of laser or intraocular surgery. METHODS: The modified van Herick grading system was used to grade the peripheral anterior chamber depth (ACD) clinically. The SPAC was used to assess ACD, and this was graded categorically as S (suspect angle closure), P (potential angle closure), or N (normal) and numerically from 1 to 12. One randomly selected eye of each subject underwent examination with the modified van Herick grading, SPAC, Goldmann applanation tonometry, optic disc examination, and gonioscopy. The SPAC measurements, modified van Herick grades (0%, 5%, 15%, 25%, 40%, 75%, and > or =100% of corneal thickness), and gonioscopy (graded as narrow or open) were correlated using the Spearman correlation coefficient. The receiver operating characteristics of the 2 methods to detect angle closure also were compared. MAIN OUTCOME MEASURES: Grading of ACD by the SPAC, the modified van Herick system, and gonioscopic grading of the angle. RESULTS: The SPAC results correlated well with the modified van Herick grading system (categorical grade, r = 0.527; numerical grade, r = 0.542; P<0.0001). For eyes graded as having narrow angles by gonioscopy, the area under the curve (AUC) for SPAC categorical grade S or P was 0.790; sensitivity and specificity were 84.9% and 73.1%, respectively. For the modified van Herick grading system, using a cutoff of peripheral ACD < or = 25% corneal thickness, the AUC was 0.872 and sensitivity and specificity were 84.9% and 89.6%. Compared with gonioscopy that found 53 of 120 cases of narrow angles, the SPAC graded more eyes as having narrow angles (63/120) than the modified van Herick system (52/120). CONCLUSIONS: The SPAC correlated well with the modified van Herick system in grading peripheral ACD. However, the SPAC appeared to overestimate the proportion of eyes with narrow angles relative to gonioscopy and the modified van Herick grading system.

Adult↗

PubMed2006

The OPA1 gene polymorphism is associated with normal tension and high tension glaucoma.

PURPOSE: To assess whether genetic polymorphisms of optic atrophy 1 (OPA1) are associated with primary open-angle glaucoma (POAG). DESIGN: Prospective case control association study. METHODS: Japanese patients with normal tension glaucoma (NTG, n = 194), and high tension glaucoma (HTG, n = 191), and 185 control subjects were analyzed for the OPA1 intervening sequence (IVS) 8+4 cystosine thymine (C/T) and IVS 8+32 thymine cystosine (T/C) polymorphisms using pyrosequencing technique. RESULTS: There was a significant difference in the OPA1 IVS 8 +32 T/C genotype frequencies between the NTG patients and control subjects (P = .0074), and the frequency of the cystosine (C) allele was significantly higher in the NTG patients compared with the control subjects (19.3% vs 11.6%, P = .0036). Adjusted for age, gender, refractive error, and intraocular pressure, an almost two-fold increased risk of NTG (P = .004, odds ratio 2.27, 95% confidence interval 1.30 to 3.97) was found with the OPA1 IVS 8 +32 C allele. Although there was no significant difference in the OPA1 IVS 8 +32 T/C genotype frequencies between the HTG patients and control subjects (P = .24), the age at the time of diagnosis (53 +/- 11.0 years, median value +/- median absolute deviation) in the HTG patients with the OPA1 IVS 8 +32 C allele was significantly younger than that (57 +/- 12.0 years) in the HTG patients without C allele (P = .048). CONCLUSIONS: The OPA1 IVS 8 +32 T/C polymorphism is associated with NTG, and may be used as a marker for this disease association. This polymorphism also influences the phenotypic feature in patients with HTG and should be considered to be a genetic risk factor not only for NTG, but also for HTG.

Aged↗

PubMed2006

Methylenetetrahydrofolate reductase gene polymorphisms c.677C/T and c.1298A/C are not associated with open angle glaucoma.

PURPOSE: To assess whether or not the c.677C/T and c.1298A/C genetic polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene are associated with open angle glaucoma (OAG). METHODS: Genomic DNA was examined in a cohort of 131 Japanese patients with normal tension glaucoma (NTG), 133 patients with primary open angle glaucoma (POAG), and 106 control subjects. The mean age at the time of blood sampling was 62.8+/-13.3 years (mean+/-SD) in the patients with NTG, 61.8+/-15.4 years in the patients with POAG, and 65.0+/-10.5 years in the control subjects. MTHFR c.677C/T and c.1298A/C genotype and allele frequencies were determined using pyrosequencing analysis, and the findings were compared between the OAG patients and control subjects. The frequencies of compound MTHFR c.677C/T and c.1298A/C genotypes were also compared between OAG patients and control subjects. RESULTS: No significant differences were observed (p>0.05, chi2 test or Fisher's exact test) regarding the MTHFR c.677C/T genotype (TT: 14.5%, CT: 44.3%, CC: 41.2% for patients with NTG; TT: 20.3%, CT: 41.4%, CC: 38.3% for patients with POAG; TT: 17.9%, CT: 36.8%, CC: 45.3% for control subjects) and c.1298A/C (CC: 0%, AC: 38.9%, AA: 61.1% for patients with NTG; CC: 2.3%, AC: 32.3%, AA: 65.4% for patients with POAG; CC: 0.9%, AC: 41.5%, AA: 57.6% for control subjects). There were no allele frequencies between the NTG or POAG patients and the control subjects. In addition, no significant differences (p>0.05, chi2 test) were found in the frequencies of the compound MTHFR c.677C/T and c.1298A/C genotypes between the NTG or POAG patients and the control subjects. CONCLUSIONS: The MTHFR c.677C/T and c.1298A/C polymorphisms were not found to be associated with NTG and POAG. Further studies in the different ethnic populations should be performed to elucidate the relationship between MTHFR and OAG.

Adenine↗

PubMed2006

Neuroprotective effect of latanoprost on rat retinal ganglion cells.

BACKGROUND: To investigate the neuroprotective effect of intravitreal administration of latanoprost on retinal ganglion cell (RGC) damage induced by N-methyl-D-aspartic acid (NMDA) or optic nerve axotomy. METHODS: Using Sprague-Dawley rats, retinal ganglion cell damage was induced by either intravitreal administration of NMDA or optic nerve axotomy. Latanoprost at doses of 0.03, 0.3, 3, 30 and 300 pmol was administered intravitreally before NMDA injection or optic nerve axotomy. Retinal damage was evaluated by counting the number of surviving RGCs retrogradely labeled with fluorogold under the microscope. RESULTS: Seven days after the NMDA injury, the number of surviving RGCs was significantly increased at doses of more than 30 pmol atanoprost (846+/-178 cells/mm(2 ) P=0.0166) compared with vehicle control (556+/-122 cells/mm(2)). Ten days after the optic nerve axotomy, the number of surviving RGC was significantly increased even at a dose of 0.3 pmol (815+/-239 cells/mm(2), P=0.0359) compared with control (462+/-75 cells/mm(2)). CONCLUSIONS: Intravitreal administration of latanoprost has a neuroprotective effect on rat RGC damage induced by either NMDA or optic nerve axotomy, while its pharmacological features are different.

Animals↗

PubMed2006

Frame shuffling: a novel method for in vitro protein evolution.

We describe 'frame shuffling', a novel method for preparing artificial protein libraries. With this method, a Y-family DNA polymerase known to introduce frame shift mutations at high rates is utilized to scramble the reading frames of a parental gene. The resultant progeny produce mutant proteins having segmental sequence changes. Such frame-shuffled mutant proteins exhibit physicochemical properties that differ from those of proteins obtained using conventional mutagenesis.

Amino Acid Sequence↗

PubMed2006

The effect of unoprostone isopropyl on Ca2+ release-activated Ca2+ currents in cultured monkey trabecular meshwork cells and ciliary muscle cells.

PURPOSE: The aim of this study was to investigate the effect of unoprostone isopropyl (UF- 021) on Ca2+ release-activated Ca2+ (CRAC) currents in cultured monkey trabecular meshwork (TM) cells and to compare the inhibitory effects on CRAC in cultured monkey ciliary muscle (CM) cells. METHODS: Both TM and CM cells were isolated from monkey eyes, and each was grown in monolayer cell cultures. To measure changes in intracellular Ca2+ concentrations ([Ca2+]i), both types of cells were labeled with fluo-3 acetoxymethylester (AM) as a calcium indicator for 30 min at 25 degrees C and imaged with a confocal laser scanning microscope. After depletion of the intracellular Ca2+ stores with 1 microM thapsigargin and 1 mM EGTA containing Ca2+-free external solution, exposure to 2 mM Ca2+-containing external solution induced a sudden increase in [Ca2+]i, which was defined as the CRAC current. RESULTS: In both TM and CM cells, CRAC currents were observed and were well suppressed by unoprostone-free acid (M1 metabolite). In the TM cells, 3 microM M1 metabolite suppressed the CRAC current. In contrast, in the CM cells, the CRAC current was suppressed by 100 microM M1 metabolite, but not by 10 microM or less. The half maximal inhibition concentration of M1 metabolite was 24.8+/-9.8 microM in TM cells and 183+/-30.6 microM in CM cells. CONCLUSIONS: These findings indicate that there are CRAC channels in both TM and CM cells, and the influx of [Ca2+]i through the CRAC channels is suppressed by M1 metabolite. The inhibitory effect of M1 metabolite on CRAC currents was more prominent in TM cells than in CM cells. Suppression of the Ca2+ influx through CRAC channels by M1 metabolite is thought to regulate muscle tone in TM and CM cells. Therefore, CRAC inhibition by M1 metabolite may contribute to reduction of intraocular pressure.

Aniline Compounds↗

PubMed2006

Effects of small-incision phacoemulsification and intraocular lens implantation on anterior chamber depth and intraocular pressure.

PURPOSE: To examine prospectively the effects of small-incision phacoemulsification and intraocular lens implantation (PEA+IOL) on anterior chamber depth (ACD) and intraocular pressure (IOP) using a newly developed scanning peripheral ACD analyzer (SPAC). MATERIALS AND METHODS: Twenty-eight eyes of 21 patients who underwent PEA+IOL without any complications were examined and divided into 7 eyes each of grades 1 to 4 according to the Van Herick technique. The SPAC measured ACD consecutively from the vicinity of the pupil center to the periphery at 0.4-mm intervals. Changes in ACD and IOP as a result of PEA+IOL were investigated, and the factors contributing to the changes in ACD and IOP were examined. RESULTS: PEA+IOL increased ACD significantly at all groups. The average changing rates were 3.19 +/- 0.67 times (Van Herick grade 1), 2.00 +/- 0.80 times (Van Herick grade 2), 1.92 +/- 0.32 times (Van Herick grade 3), and 1.36 +/- 0.65 times (Van Herick grade 4), respectively. The closer to the pupil center the measurement point was, the larger was the increase in ACD. However, the rates of increase in ACD were similar among the measurement points. The increases in ACD were significantly large in patients having a shallow preoperative ACD and a small optic axis length. The IOP reduction became significantly large in eyes with a shallow preoperative ACD. CONCLUSIONS: The SPAC enabled quantitative measurement of changes in ACD from the vicinity of the pupil center to the periphery as a result of PEA+IOL. Changes in ACD resulting from PEA+IOL were thought to exert a greater effect on aqueous humor outflow facility as the postoperative ACD became shallower.

Aged↗

PubMed2006

Comparison between newly developed scanning peripheral anterior chamber depth analyzer and conventional methods of evaluating anterior chamber configuration.

PURPOSE: To compare the newly developed scanning peripheral anterior chamber depth analyzer (SPAC) with the Van Herick technique, the Shaffer grading system, and ultrasound biomicroscopy (UBM), in terms of accuracy of measurement of peripheral anterior chamber depth (ACD). METHODS: The subjects were well-controlled glaucoma patients who were being treated at the University of Yamanashi Hospital. Ten eyes from each of the 4 groups classified as Shaffer grades 1 to 4 were evaluated by SPAC, the Van Herick technique, and UBM. All measurements were performed independently on the temporal side in a masked fashion. SPAC evaluated ACD consecutively from the pupil center to the limbus at 0.4 mm intervals. UBM measurements were carried out at a depth of 500 mum (angle-opening distance 500) from the scleral spur. A dummy eye was used for evaluating SPAC measurement accuracy. RESULTS: The results of SPAC measurement were well correlated with those of the Van Herick technique and the Shaffer grading system. The SPAC measurement results were also significantly correlated with angle-opening distance 500. The correlation coefficients at distances of 2, 4, 4.8, and 5.6 mm from the pupil center were r=0.68, 0.69, 0.69, and 0.61, respectively, and the P values of all the correlations were less than 0.0001. Study of the dummy eye revealed that SPAC has high accuracy for measuring ACD and that the coefficient variances were less than 1.0% at all measured points. CONCLUSIONS: The results of SPAC measurement correlate well with those of the conventional methods.

Aged↗

PubMed2006

Development of a fully automated peripheral anterior chamber depth analyzer and evaluation of its accuracy.

PURPOSE: The aim of this study was to improve the scanning peripheral anterior chamber depth analyzer (SPAC) for measuring anterior chamber depth (ACD), differentiating eyes with shallow anterior chamber, and automatically categorizing eyes into subgroups based on the ACD values. We also investigated its accuracy for measuring anterior ocular biometry. MATERIALS AND METHODS: The improved SPAC system was equipped with an auto-focusing system for measuring ACD from the optical axis to the limbus without contacting the ocular surface, in addition to an auto-measuring system for determining central corneal thickness (CCT) and corneal radius of curvature (CRC). This system was also equipped with an auto-diagnosing program for differentiating eyes with narrow angle and an auto-classifying program for categorizing eyes into 12 subgroups according to the ACD values. A dummy eye was used for investigating the measurement accuracy and reproducibility of CCT, CRC, and ACD. Measurement duration and clinical availability were investigated using healthy subjects and glaucoma patients. RESULTS: The SPAC-measured CCT, CRC, and ACD values were very similar to the theoretical values obtained from the dummy eye and their coefficients of variation were less than 1%. This system completed ACD measurement in 15.6+/-1.0 seconds and the mean coefficient of variation of ACD was 8.8+/-2.3%. The improved SPAC system successfully differentiated eyes with narrow angle from those with wide open angle. CONCLUSIONS: The improved SPAC system can measure ACD easily with good accuracy and reproducibility, and is considered to be suitable for evaluating ACD in routine examinations and screening eyes with narrow angle.

Adult↗

PubMed2006

Role of apoptosis signal-regulating kinase 1 in stress-induced neural cell apoptosis in vivo.

Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase that plays an important role in oxidative stress-induced apoptosis. In the present study, we used ASK1 knockout (KO) mice to examine the possibility that ASK1 is involved in the neural cell apoptosis that occurs during retinal development and ischemic injury. ASK1 was expressed in retinal neurons, including retinal ganglion cells (RGCs), but retinal structure and extent of cell death during development were normal in ASK1 KO mice. On the other hand, the strain was less susceptible to ischemic injury, and the number of surviving retinal neurons was significantly increased compared with that in wild-type mice. Interestingly, ischemia-induced phosphorylation of p38 mitogen-activated protein kinase (p38), which mediates RGC apoptosis, was almost completely suppressed in ASK1 KO mice. In such retinas, the numbers of cleaved caspase-3- and TUNEL-positive neurons were apparently decreased compared with those in wild-type mice. Furthermore, cultured RGCs from ASK1 KO mice were resistant to H(2)O(2)-induced apoptosis. Our findings suggest that ASK1 is involved in the neural cell apoptosis after various kinds of oxidative stress. Thus, inhibition of the ASK1-p38 pathway could be useful for the treatment of neurodegenerative diseases including glaucoma.

Animals↗

PubMed2005

Different expression role among glutamate transporters in rat retinal glial cells under various culture conditions.

Using cultured rat retinal glial cells, the changes in the expression of glutamate transporters (GLTs) under such conditions as the degree of confluence of the cells, hypoxia, glutamate loading, and potassium loading, were assessed. After the retinal glial cells were isolated from 3-day-old Sprague-Dawley rats, GLAST, GLT-1, and EAAC1 mRNA expression was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and their protein expression was confirmed by Western blot analysis and immunostaining. Changes in the expression of the GLTs at 6 h after passage and at confluence, during culture in 5% oxygen, during glutamate loading and during potassium loading were assessed using real-time PCR. Although the GLAST mRNA expression was increased during glutamate and potassium loading, no changes in the expression were observed during hypoxia and at confluence. By contrast, the GLT-1 mRNA expression was increased during hypoxia and at confluence, but not during glutamate and potassium loading, and the EAAC1 mRNA expression was not changed only during glutamate loading. The expression of EAAC1 in the cultured retinal glial cells was confirmed. The expression of the GLTs varied according to the environment and the type of load suggests that the involvement of the GLTs in retinal physiology and pathology varies depending on the subtype.

Animals↗

PubMed2005

The apolipoprotein E gene polymorphism is associated with open angle glaucoma in the Japanese population.

PURPOSE: To assess whether genetic polymorphisms of the apolipoprotein E (APOE) gene are associated with open angle glaucoma (OAG) in the Japanese population. METHODS: Genomic DNA was examined in a cohort of 310 Japanese patients with OAG and 179 control subjects. The average age was 63.5+/-14.4 years (mean+/-SD) for the OAG patients and 65.5+/-11.6 years for the control subjects. The presence or absence of OAG in patients and controls was based on clinical examination and/or ophthalmic records. The APOE allele frequency (epsilon2, epsilon3, and epsilon4 alleles) was studied by restriction fragment length polymorphism, and compared between OAG patients and control subjects. The association between the intraocular pressure (IOP) and the APOE alleles was also evaluated. RESULTS: There was a significant difference in the APOE genotype frequencies between these groups (p=0.0006 chi2 test). The frequencies of the epsilon2 and epsilon4 alleles were significantly lower in the OAG patients (epsilon2: 2.6%; epsilon4: 6.0%) compared to the control subjects (epsilon2: 5.0%, p=0.048; epsilon4: 10.6%, p=0.012; Fisher's exact test). The frequency of the epsilon3 allele was significantly higher in the OAG patients (91.4%) compared to the control subjects (84.4%, p=0.0010; Fisher's exact test). Adjusted for age, gender, and IOP, an appropriate three fold reduction in OAG risk (odds ratio [OR] 0.29, 95% confidence interval [CI] 0.10 to 0.80; p=0.018) was found with the epsilon2 allele and a two fold increased risk of OAG (OR 1.97, 95% CI 1.06 to 3.67; p=0.033) was found with the epsilon3 allele. The maximum IOP (18.3+/-6.0 mm Hg) in patients with the epsilon4 allele was significantly lower than that (21.3+/-9.1 mm Hg) in patients without the epsilon4 allele (p=0.006, Student's t-test). CONCLUSIONS: The APOE gene polymorphism is associated with OAG in the Japanese population. Further studies in the other ethnic populations should be performed to elucidate the relationship between APOE and OAG.

Aged↗

PubMed2005

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

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

Animals↗

PubMed2005

The HU knot: a new sliding knot for arthroscopic surgery.

Sliding knots are commonly used in arthroscopic knot tying. The Surgical knot as a hand-tied knot is very secure. We found that the Surgical knot could be used as a sliding knot. We have modified the Surgical knot to include a self-locking loop. A new sliding knot for arthroscopic surgery, the HU knot, is described. By tensioning the loop strand, the self-locking loop creates a snug knot without sliding backward. The HU knot provides great security.

Arthroscopy↗

PubMed2004

Mutations in the optineurin gene in Japanese patients with primary open-angle glaucoma and normal tension glaucoma.

The optineurin gene (OPTN) was identified as a gene that causes primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG). To investigate the frequency of sequence changes in OPTN in Japanese glaucoma patients, single-strand conformation polymorphism analysis and subsequent sequence analysis were performed for genotyping OPTN in 165 unrelated Japanese patients with POAG and 148 patients with NTG, with 196 control subjects without glaucoma as reference subjects. Out of four mutations reported to be associated with risk and to cause disease in Caucasian patients, sequence alterations in 458G > A and 691_692insAG were not detected in any investigated Japanese patients with glaucoma, and alterations in 1944G > A and 603T > A, were present in similar frequencies in glaucoma patients and control subjects. The current results suggest that there may be certain racial differences between Japanese and Caucasians with respect to OPTN genotypes.

Adult↗

PubMed2004

Effects of transforming growth factor-beta 1 on the early stages of healing of the Achilles tendon in a rat model.

We studied the effects of transforming growth factor-beta 1 (TGF-beta 1) on the genetic expression of procollagen type I and III and its effects on structural properties in the early stages of healing in rat Achilles tendon. The Achilles tendons in 90 rats were transsected and repaired immediately. TGF-beta 1 dissolved in phosphate-buffered saline was injected locally at the repair site using two different doses, and outcomes in both groups were compared to that in the control group given phosphate-buffered saline only. Five animals in each group were killed at one, two, and four weeks postoperatively, and the healing tendon was evaluated. A dose-dependent increase in the expression of procollagen type I and III mRNA was found one week postoperatively. The failure load and stiffness of the healing tendon were increased by TGF-beta 1 at two and four weeks.

Achilles Tendon↗

PubMed2004

Association of magnetic resonance imaging of anterior optic pathway with glaucomatous visual field damage and optic disc cupping.

PURPOSE: To investigate the association of magnetic resonance imaging (MRI) of anterior optic pathway with glaucomatous visual field damage and optic disc cupping. SUBJECTS AND METHODS: Twenty-three healthy volunteers (controls) and 31 glaucoma patients (14 with primary open angle glaucoma and 17 with normal tension glaucoma) were enrolled. All the participants showed no abnormal signs in their intracranial space and optic tract causing optic nerve atrophy and visual field defect, as confirmed by MRI. Multislice T1-weighted spin-echo imaging was performed in the sagittal plane followed by the coronal plane. MRI enabled the evaluation of the diameter of the optic nerve located in the retro-bulb space and the height of the optic chiasm in an observer-masked fashion. The MRI data were compared with the mean deviation (MD) score of the full threshold static visual field test and the optic cup-disc ratio (C/D ratio). RESULTS: The optic nerve diameter was significantly smaller in glaucoma patients (2.25 +/- 0.33 mm) than in controls (2.47 +/- 0.24 mm) and the height of the optic chiasm was significantly shorter in glaucoma patients (2.12 +/- 0.37 mm) than in controls (2.77 +/- 0.36 mm). The optic nerve diameter showed significant correlation with MD score (r = 0.547, P = 0.001) and C/D ratio (r = 0.407, P = 0.009). These correlations are similar to that between MD score and C/D ratio (r = 0.490, P = 0.001). The height of the optic chiasm showed significant correlation with MD score (r = 0.503, P = 0.01) and low correlation with C/D ratio (r = 0.339, P = 0.113). CONCLUSION: Glaucoma affects the anterior visual pathway anterogradely at least up to the optic chiasm, and these morphologic changes in the anterior visual pathway are correlated with glaucomatous optic nerve damage. MRI of the anterior visual pathway may be a good tool for evaluating glaucomatous damage objectively.

Adult↗

PubMed2004

Effects of bunazosin hydrochloride on ciliary muscle constriction and matrix metalloproteinase activities.

PURPOSE: To clarify the mechanism by which bunazosin hydrochloride (BZ), a selective alpha1-adrenoceptor antagonist, increases uveoscleral outflow. METHODS: The effects of BZ on matrix metalloproteinase (MMP) activities in cultured monkey ciliary muscle cells, and on phenylephrine hydrochloride-induced constriction in bovine ciliary muscles, were examined. Also, the possible additive ocular hypotensive effects of BZ and latanoprost (LP) were evaluated in ocular normotensive monkeys. RESULTS: Although BZ at 10 to 10 M did not increase MMP-2, -3, and -9 activities in the culture medium of ciliary muscle cells, BZ at 10 to 10 M inhibited phenylephrine hydrochloride-induced constriction in ciliary muscles. The maximal reduction in intraocular pressure of concomitant administration of BZ and LP was greater than that of BZ alone and tended to be greater than that of LP alone. CONCLUSION: These findings, in normotensive monkeys, indicate that the mechanism whereby BZ increases uveoscleral outflow is independent of an effect on MMPs and is partly due to relaxation of the ciliary muscle. This effect is different from that of LP, which might help to explain the finding that topical concomitant administration of BZ and LP increased AUC(0-6h) value (IOP reduction) to 201% and 145% of BZ and LP given alone, respectively.

Adrenergic alpha-Antagonists↗