Biomedical subjects

M Araie

Publications and source records attributed to M Araie.

At least 37 records · Page 2Linked to original sources

PubMed2001

Mathematical and optimal clustering of test points of the central 30-degree visual field of glaucoma.

PURPOSE: To determine a mathematically optimal sector pattern of the central 30 degree visual field for the follow-up of glaucomatous visual field change based on a large number of actual visual field test data of patients with glaucoma. METHODS: Visual field test data obtained from 1,039 eyes of 1,039 patients with open-angle glaucoma (OAG) using the 30-2 program of the Humphrey Field Analyzer were used for sectorization of the central 30 degree visual field. Of the 1,039 visual field data, 698 (modeling data) were used for determining the sector pattern and 341 (testing data) for checking the sector pattern. The modeling data were further divided into three groups according to the mean deviation (MD) (MD > or = -10 dB, -20 < or = MD < -10 dB, and MD < -20 dB), and the sector pattern was constructed from visual field data of each group using a clustering procedure called VARCLUS. The testing data were used for determining the optimal sector pattern. In a separate set of repeated visual field data of 303 patients with OAG, the fluctuation of MD, sector values of each sector determined, and total deviation of each test point were calculated and compared. RESULTS: The sector pattern constructed from visual field data of MD > or = -10 dB summarized the visual field performance most effectively. The fluctuation of the sector value of each sector was roughly 1.5 times smaller than the total deviation of each test point. CONCLUSION: The sector pattern determined may be useful in analyses of the visual field data of patients with glaucoma.

Glaucoma, Open-Angle↗

PubMed2001

Frequency doubling technology and confocal scanning ophthalmoscopic optic disc analysis in open-angle glaucoma with hemifield defects.

PURPOSE: To evaluate the potential of frequency doubling technology for detecting early glaucomatous damage. PATIENTS AND METHODS: Forty-nine eyes of 49 patients with open-angle glaucoma with visual field defects only in one hemifield according to the Humphrey Field Analyzer 30-2 program were included. Forty-five healthy patients were also included as control subjects. In each patient, frequency doubling technology with the threshold N-30 program and optic disc analysis using the Heidelberg Retina Tomograph was performed. Frequency doubling technology test results and the Humphrey Field Analyzer test results were compared. Optic disc parameters corresponding to the hemifield designated intact by the Humphrey Field Analyzer were compared between the eyes in which the hemifield was normal by frequency doubling technology and those in which the hemifield was abnormal. RESULTS: Forty-one percent of the 49 hemifields designated intact by the Humphrey Field Analyzer were abnormal based on frequency doubling technology, whereas 98% of the 49 hemifields designated defective by the Humphrey Field Analyzer were abnormal and 12% of the 90 hemifields designated intact by the Humphrey Field Analyzer were abnormal in healthy patients. The percentage of the hemifields designated abnormal by frequency doubling technology was significantly higher than that in healthy patients (P < 0.001). The rim volume was significantly smaller in eyes with abnormal results based on frequency doubling technology than in eyes with normal results (P < 0.05, paired t test, with Bonferroni correction for multiple comparison). CONCLUSION: Frequency doubling technology can detect glaucomatous damage earlier than conventional static perimetry can.

False Positive Reactions↗

PubMed2001

Long-term follow-up of initial 5-fluorouracil trabeculectomy in primary open-angle glaucoma in Japanese patients.

PURPOSE: To evaluate the long-term efficacy and safety of initial trabeculectomy with subconjunctival 5-fluorouracil in Japanese patients with primary open-angle glaucoma. SUBJECTS AND METHODS: Clinical records of 117 eyes from 117 patients with records of up to 14 years were retrospectively analyzed using the appropriate statistical methods. RESULTS: The mean follow-up period was 6.2 +/- 3.6 years. Criteria for successful intraocular pressure control and success probability by Kaplan-Meier method at 12 years were intraocular pressure < 21 mm Hg without medication plus a 30% or more reduction in intraocular pressure, 50.4 +/- 5.2% (SE) 38.2 +/- 5.3%; and intraocular pressure < 16 mm Hg without medication plus a 30% or more reduction in intraocular pressure, 45.9 +/- 5.1% (36.5 +/- 5.2%). Cox multiple regression analysis showed that a younger age was associated with a higher success probability (P <0.01). Eyes with lower postoperative intraocular pressure tended to show more positive value of the MD slope (P = 0.0669), whereas 7% of successfully treated eyes showed a negative postoperative MD slope (P < 0.1). The probabilities for developing bleb leaks and bleb-related infections in eyes with a functioning bleb were 28.9 +/- 12.5% and 13.0 +/- 10.4% at 12 years. CONCLUSION: Trabeculectomy with 5-fluorouracil as an initial surgery in Japanese patients with primary open-angle glaucoma was effective for long-term control of glaucoma. However, the probability of late-onset bleb-related complications was not low in eyes with a functioning bleb, stressing the importance of constant care regarding bleb status.

Adult↗

PubMed2001

Molecular basis of ocular abnormalities associated with proximal renal tubular acidosis.

Proximal renal tubular acidosis associated with ocular abnormalities such as band keratopathy, glaucoma, and cataracts is caused by mutations in the Na(+)-HCO(3)(-) cotransporter (NBC-1). However, the mechanism by which NBC-1 inactivation leads to such ocular abnormalities remains to be elucidated. By immunological analysis of human and rat eyes, we demonstrate that both kidney type (kNBC-1) and pancreatic type (pNBC-1) transporters are present in the corneal endothelium, trabecular meshwork, ciliary epithelium, and lens epithelium. In the human lens epithelial (HLE) cells, RT-PCR detected mRNAs of both kNBC-1 and pNBC-1. Although a Na(+)-HCO(3)-cotransport activity has not been detected in mammalian lens epithelia, cell pH (pH(i)) measurements revealed the presence of Cl(-)-independent, electrogenic Na(+)-HCO(3)-cotransport activity in HLE cells. In addition, up to 80% of amiloride-insensitive pH(i) recovery from acid load in the presence of HCO(3)(-)/CO(2) was inhibited by adenovirus-mediated transfer of a specific hammerhead ribozyme against NBC-1, consistent with a major role of NBC-1 in overall HCO(3)-transport by the lens epithelium. These results indicate that the normal transport activity of NBC-1 is indispensable not only for the maintenance of corneal and lenticular transparency but also for the regulation of aqueous humor outflow.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed2001

Neuroprotective effect and intraocular penetration of nipradilol, a beta-blocker with nitric oxide donative action.

PURPOSE: To investigate the effect of nipradilol, an alpha(1),beta-blocker with a nitric oxide donative action, on N:-methyl-D-aspartate (NMDA)-induced retinal damage in rats and to determine whether topically instilled nipradilol penetrates the ipsilateral posterior retina-choroid at pharmacologically active concentrations in rabbits. METHODS: To determine effects on NMDA-induced damage, drugs were injected alone or with NMDA into the vitreous of one eye, and cell loss in the ganglion cell layer (GCL) and thinning of the retinal neural cell layers were histologically evaluated. To evaluate posterior penetration, first, [(14)C]-nipradilol was instilled, and its tissue concentration was measured. Second, nipradilol or timolol was instilled, and their effects on intravitreal injection of endothelin-1-induced retinal artery contraction were compared, to evaluate whether a pharmacologically active level of nipradilol penetrates the inner limiting layer by topical application. RESULTS: Intravitreous injection of NMDA reduced cell numbers in the GCL and the thickness of the inner plexiform layer (IPL) to 50.4% +/- 2.6% and 47.8% +/- 4.9% (n = 8) of control, respectively. Nipradilol alone had no effect. Coadministration of nipradilol with NMDA reduced cell numbers in the GCL and IPL thickness to 67.8% +/- 2.2% and 74.4% +/- 5.2% of control, respectively (P: < 0.05-0.01). Sodium nitroprusside, but not timolol or bunazosin, also significantly prevented the NMDA-induced reduction of cell numbers in the GCL and IPL thickness. Radioactivity of nipradilol was found in the ipsilateral posterior retina-choroid at 318.6 +/- 42.9 ng/g (n = 4), which was significantly higher than in the contralateral control (107.4 +/- 21.8 ng/g). Topical application of nipradilol, but not timolol, significantly suppressed the endothelin-1-induced contraction of the retinal artery (83.95% +/- 8.15% and 35.24% +/- 5.62% of baseline vessel diameter for nipradilol and timolol, respectively). CONCLUSIONS: Nipradilol suppressed the NMDA-induced retinal damage in rats for which nitric oxide released from nipradilol may be responsible. Posterior penetration studies suggested that an effective concentration of nipradilol reached the posterior retina after topical application.

Adrenergic alpha-Antagonists↗

PubMed2001

Rapid detection and typing of oculopathogenic strain of subgenus D adenoviruses by fiber-based PCR and restriction enzyme analysis.

PURPOSE: To develop a new detection and typing method of oculopathogenic strains of subgenus D adenoviruses directly from conjunctival scrapings by a combination of polymerase chain reaction (PCR) and restriction enzyme analysis (REA). METHODS: A new PCR method using primer pairs of AF2/AR2, which are specific for the fiber genes, were developed to amplify 1150-bp products from nine oculopathogenic prototypes of subgenus D adenoviruses. Amplicons were cleaved with three restriction enzymes: DdeI, HinfI, and RsaI. Clinical specimens of 102 conjunctival scrapings were also evaluated by this PCR method. Restriction patterns of prototypes were used for the typing of clinical samples. Detection limit was determined by the PCR amplification of a known amount of purified adenovirus serotype 8 DNA. RESULTS: A novel PCR method based on the fiber genes allowed the amplification of nine oculopathogenic serotypes of subgenus D (Ad8, Ad9, Ad15, Ad17, Ad19, Ad22, Ad28, Ad37, and Ad39). As little as 38.4 fg of adenovirus type 8 could be detected by this method. Positive results were obtained from 48 of 102 samples (47%) by both hexon- and fiber-based PCR, whereas only 29 of 102 (28.4%) yielded positive results by culture isolation/neutralization test (NT). All positive specimens (29 samples) of culture isolation and PCR-RFLP methods showed positive results by our new fiber-based PCR method, and no positive products were detected from other subgenus of adenovirus or nonadenoviral DNA. CONCLUSIONS: A newly developed fiber-based PCR-REA method for the detection and typing of adenoviruses is faster than any former PCR methods. This all-in-1-day detection and typing method will be quite useful to the rapid diagnosis of subgenus D adenovirus infection.

Adenovirus Infections, Human↗

PubMed2001

Novel cytochrome P4501B1 (CYP1B1) gene mutations in Japanese patients with primary congenital glaucoma.

PURPOSE: To investigate CYP1B1 gene mutations in Japanese patients with primary congenital glaucoma (PCG). METHODS: Sixty-five unrelated Japanese patients with PCG were screened by PCR-single-strand conformational polymorphism (SSCP) analysis followed by direct sequencing. No patients were offspring of consanguineous marriages, a common occurrence among patients in previous reports. PCG haplotypes were constructed with intragenic polymorphisms in affected individuals. Three-dimensional atomic structures of human CYP1B1 and four mutant CYP1B1 sequences representing missense mutations were assembled using homology modeling and were regularized by an energy-minimization procedure. RESULTS: Eleven novel mutations, including seven definite and four probable mutations, were detected in 13 (20%) of the 65 unrelated patients. Of the seven definite mutations, three were predicted to truncate the CYP1B1 open reading frame. The other four were missense mutations (Asp192Val, Ala330Phe, Val364Met, and Arg444Gln), all located in conserved core structures determining proper folding and heme-binding ability of cytochrome P450 molecules. Molecular modeling demonstrated that two of four mutations in positions 330 and 364 were structurally neutral, but Arg444Gln caused significant structural change. Of the four probable mutations, three were missense (Val198Ile, Val320Leu, and Glu499Gly); the other was a base substitution in the noncoding region of exon 1. CONCLUSIONS: The 11 varied CYP1B1 mutations found in 13 unrelated Japanese patients with sporadic occurrence of PCG represent an allelic heterogeneity and may be unique to a specific population.

Amino Acid Sequence↗

PubMed2001

Effects of retinal glial cells on isolated rat retinal ganglion cells.

PURPOSE: The effect of retinal glial cells on retinal ganglion cell (RGC) survival was investigated in cocultures of pure, isolated retinal glial cells with pure, isolated RGCs. METHODS: RGCs from 2-day-old rats were cocultured for 48 hours, avoiding direct contact between cell types, with either nonconfluent retinal glial cells from 3-day-old rats or confluent retinal glial cells from 3-day-old, 12-day-old, or 1-year-old rats. Survival of RGCs was evaluated by flow cytometry. Amino acids were determined in culture medium. The effects of glutamate antagonists, 6-cyano-7-nitroquinoxaline-2,3-dione and MK801, a nitric oxide (NO) scavenger, 2-(4-carboxyphenyl)-4,4,5,5tetramethylimidazoline-1-oxyl-3-oxide potassium salt (c-PTIO), and an NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), were examined. RESULTS: Nonconfluent retinal glial cells significantly reduced the survival of small and large RGCs, but confluent retinal glial cells reduced the survival of only small RGCs, regardless of the rat's age at the time of retinal glial cell harvesting. Profiles of some amino acids significantly varied, depending on the culture condition. Cocultures of RGCs with nonconfluent retinal glial cells released significantly more glutamate into the medium than cocultures of RGCs with confluent retinal glial cells or RGCs in pure culture. The glutamate antagonists improved the survival of RGCs cocultured with nonconfluent retinal glial cells, especially when the two were administered in combination, and in the case of large RGCs. c-PTIO and L-NAME, also improved the survival of RGCs cocultured with nonconfluent retinal glial cells. CONCLUSIONS: Adverse effects of retinal glial cells on the survival of RGCs varied by size of the RGCs and retinal glial cell confluence. Glutamate and NO may be involved in retinal glial cell-related antisurvival effects.

Animals↗

PubMed2001

Effects of topical latanoprost on optic nerve head circulation in rabbits, monkeys, and humans.

PURPOSE: To evaluate the effect of topically administrated latanoprost on optic nerve head (ONH) circulation in Dutch rabbits, cynomolgus monkeys, and normal humans. METHODS: The ONH tissue blood velocity (NB(ONH)) was determined using the laser speckle method. Latanoprost (0.005%, 30 microl) was instilled into one eye, and vehicle into the other eye as a control. In rabbits, NB(ONH) was measured for 90 minutes after a single instillation and before and after a 7-day once-daily instillation regimen. In monkeys, NB(ONH) was measured before and after 1, 4, and 7 days of a once-daily instillation regimen. The effect of intravenous indomethacin on the latanoprost-induced NB(ONH) change was also studied in rabbits and monkeys. In humans, the time-course changes in NB(ONH) were measured for 4.5 hours before and after a 7-day once-daily instillation regimen. Intraocular pressure (IOP) and systemic parameters were simultaneously studied in each experiment. All measurements were performed by investigators masked to the experimental condition. RESULTS: Latanoprost significantly increased NB(ONH) 10% to 19% in treated eyes after a single instillation (P = 0.035) or 7-day instillation regimen (P = 0.035) in rabbits, after a 4-day (P = 0.035) or 7-day (P = 0.035) instillation regimen in monkeys, and after a 7-day (P = 0.013) instillation regimen in humans, whereas there were no significant changes in the vehicle-treated eyes in any of the experiments (P > 0.5). Pretreatment with indomethacin (5 mg/kg) abolished the NB(ONH) increase but not the IOP reduction in latanoprost-treated eyes in rabbits and monkeys. IOP remained unchanged in both eyes in rabbits (P > 0.4), whereas it significantly decreased only in latanoprost-treated eyes in monkeys (P < 0.05) and humans (P < 0.05). CONCLUSIONS: Topical latanoprost significantly increased ONH blood velocity only in treated eyes in rabbits, monkeys, and humans. This effect was independent of the IOP-reducing effect of latanoprost and probably was associated with local penetration of the drug and the production of endogenous prostaglandins.

Administration, Topical↗

PubMed2000

Neurotrophic function of conditioned medium from human amniotic epithelial cells.

Human amniotic epithelial cells (HAEC) may have pluripotent function because they are formed from the epiblast cells at the 8th day of fertilization. Previously, we reported that HAEC have the capacity to synthesize and release acetylcholine and catecholamine associated with the binding sites of catecholamine receptors. We show the neurotrophic function of a conditioned medium from HAEC using cultured cortical neurons of E18 rats. Extensive analyses with various techniques demonstrated that HAEC and immortalized HAEC synthesize and release brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and nerve growth factor (NGF). Other neurotrophic factors were not detected in a cultured medium of HAEC by enzyme immunoassay. Various neurotrophic factors or growth factors did not show neurotrophic effects on E18 rat neuron except for EGF. Because EGF was not detected in the conditioned medium of HAEC, these data indicate an unidentified neurotrophic factor presently that is synthesized and released from HAEC. The amniotic membrane may have a significant role in supplying neurotrophic factors to the amniotic fluid as well as neurotransmitters, suggesting an important function to the early stages of neural development in the embryo.

Amniotic Fluid↗

PubMed2000

Sinusotomy with Intraoperative Mitomycin C Administration in Selected Eyes with Advanced Glaucomatous Damage.

Purpose: The surgical outcome of sinusotomy with intra-operative mitomycin C administration (0.04%, 3 minutes) in a total of 17 selected glaucoma eyes from 14 patients with advanced glaucomatous damage was examined. Selection criteria were (1) an eye with visual field defect threatening the central fixation, while the central visual acuity of the contralateral eye was already impaired; and/or (2) an aphakic or pseudophakic eye with advanced glaucomatous damage in a patient of advanced age.Materials and Methods: Patient's age, preoperative mean deviation (Humphrey 30-2 program) and intraocular pressure (IOP) averaged 63.5 +/- 11.1 (mean +/- standard deviation) years, -18.6 +/- 6.7 (mean +/- standard deviation) dB, and 20.7 +/- 4.1 (mean +/- standard deviation) mmHg, respectively.Results: No postoperative hypotony (< 5 mmHg) or deterioration of visual acuity equal to or more than 2 lines of Ishihara Visual Acuity Chart were encountered and the mean postoperative IOP ranged between 11 and 13 mmHg up to 18 months postoperatively with less medication than preoperatively. The success was defined as IOP </= 15 mmHg without oral carbonic anhydrase inhibitors and with less medication than preoperatively. The life-table method analysis according to the above criteria yielded a success probability of 70.6 +/- 11.1 (mean +/- standard deviation) % (standard error) at 18 months postoperatively.

Journal Article↗

PubMed2000

In vivo measurement of ocular circulation with the laser speckle method-development of apparatus and application in ophthalmological research

central retinal vein was 35.5 +/- 3.2 mm/sec with a correlation coefficient between them of 0.91. In a total of 4 eyes with impending central retinal vein or artery occlusion, measurements by the laser speckle method, and CDI method were carried out. The blood velocities measured by the both methods increased along with the treatment. A good correlation between the CDI results and the laser speckle results indicates validity and clinical potential of the present laser speckle method.

Journal Article↗

PubMed2000

Usefulness of gaze tracking during perimetry in glaucomatous eyes

Purpose: To evaluate the usefulness of a new fixation monitoring system called gaze tracking in the perimetry of glaucomatous eyes. Subjects and Method: We studied the visual field of 106 eyes in 106 persons, comprising 74 eyes with open-angle glaucoma and 32 eyes with ocular hypertension. Perimetry was performed using a Humphrey Visual Field Analyzer 740/750 with a 30-2 full threshold program. We used two parameters for gaze tracking: the percentage of the time when the subject's eye deviated from the fixation target more than 3 degrees (G 3) and 6 degrees (G 6). These parameters were assessed in three groups: those with no visual field defect (group N), those with absolute visual field defect including the blind spot (group M 1), and others (group M 0).Result: The values of G 3 and G 6 were significantly correlated with the fixation loss in groups N and M 0 (P <.01). These values were not significantly correlated with the fixation loss in group M 1 (P.10). When the fixation loss was less than 20%, G 3 and G 6 values were significantly higher in group M 1 than in groups N or M 0.Conclusion: Gaze tracking is a useful fixation monitoring system particularly in the presence absolute visual field defect including the blind spot.

Journal Article↗

PubMed2000

Ets family transcription factor ESE-1 is expressed in corneal epithelial cells and is involved in their differentiation.

Involvement of an epithelium-specific transcription factor ESE-1/ESX/ELF3/jen (ESE-1) in corneal epithelial cell differentiation was investigated. ESE-1 was reported to be induced during terminal differentiation of the epidermis and primary keratinocytes and to transactivate target genes through ets binding sites. However, its expression and function in corneal epithelium have not been examined. We report here that ESE-1 is upregulated upon differentiation in mouse corneal epithelium and in immortalized human corneal epithelial cells (HCE). ESE-1 transactivates through the regulatory element of cornea-specific K12 keratin. Moreover, introduction of ESE-1 antisense RNA in HCE cells affect their differentiation. These data suggest the involvement of ESE-1 in differentiation of corneal epithelial cells.

Animals↗

PubMed2000

The acute effects of cigarette smoking on human optic nerve head and posterior fundus circulation in light smokers.

PURPOSE: To study the acute effects of cigarette smoking on tissue circulation in the optic nerve head (ONH) and posterior fundus in smokers with a short smoking history. METHODS: Ten healthy smokers whose length of smoking history was within 2 years (age 25 +/- 1 years; smoking index (number of cigarettes smoked per day x length of smoking history in years) 16 +/- 4, mean +/- SE) were included in the study. Using the laser speckle method, normalised blur (NB) value, a quantitative index of tissue blood velocity, was measured every 0.125 s and averaged over three pulses across an area located in the temporal site of the ONH free of visible surface vessels (NBONH) and across an area located halfway between the macula and the ONH with no discrete vessels visible (NBch-ret). NBONH, NBch-ret and intraocular pressure (IOP) in one randomly chosen eye, and blood pressure (BP) and pulse rate (PR) were measured before, and 1, 5, 10, 15, 20, 25, 30, 45, 60 and 90 min after sham smoking. One week later, NBONH, NBch-ret and IOP in the same eye, and BP and PR were measured after cigarette smoking according to the same time schedule as in the control experiment. RESULTS: After sham smoking, no parameter showed a significant change during the experiment. Differences in NBONH from the baseline were not significant between the smoking experiment and sham smoking experiment, while NBch-ret showed a significant difference at 30 min. Inter-group difference in the time course of the difference from baseline was significant (ANOVA, p = 0.0246, 0.0021). BP and PR were significantly increased between 1 and 20 min after smoking while IOP showed no significant change at any time of measurement. CONCLUSIONS: In light smokers, cigarette smoking showed little effect on tissue blood velocity in the ONH and slightly decreased that in the posterior fundus, suggesting a significant increase in vascular resistance in these tissues.

Adult↗

PubMed2000

Effects of semotiadil, a novel calcium antagonist, on the retina and optic nerve head circulation.

The effects of semotiadil, a novel benzothiazine calcium antagonist, on the retinal and optic nerve head (ONH) tissue circulation were evaluated using the noninvasive laser speckle method. In urethane-anesthetized Dutch or albino rabbits, before and up to 90 min following intravenous injection of 400 microg/kg semotiadil fumarate (semotiadil group) or vehicle (control group), normalized blur value, a quantitative index of tissue blood velocity, in the retina (NB(retina)) or ONH (NB(onh)), was serially obtained with monitoring intraocular pressure (IOP) and systemic parameters: arterial pressure, pulse rate, arterial blood gas, and body temperature. There were no significant differences in IOP and the systemic parameters except arterial pressure between semotiadil and control groups during the experiments. Arterial pressure showed an acute and transient drop during the first 5 min after semotiadil administration. The time courses of the normalized blur value were significantly different between semotiadil and control groups in the retina (P = 0.0001, repeated measures two-way ANOVA), but not in the ONH (P = 0.6724). Changes in NB(retina) from the baseline in the semotiadil group was significantly greater than those in the control group 50 min or later after the administration (P < 0.0500, Mann-Whitney test). NB(onh) showed no significant differences between the two groups except during the first few min when arterial pressure acutely decreased in the semotiadil group. In conclusion, intravenously injected semotiadil increased the tissue blood velocity in the retina, but not in the ONH. This vascular selectivity in the ocular neural tissues differs from those of other calcium antagonists, such as nicardipine.

Animals↗

PubMed2000

Effect of ifenprodil on aqueous humor dynamics and optic nerve head circulation in rabbits.

The purpose of this study was to study the effects of ifenprodil, a cerebral vasodilator with alpha and N-methyl-D-aspartate (NMDA) receptor antagonistic activities, on aqueous humor dynamics and optic nerve head (ONH) circulation in rabbits. Experiments were performed during the dark phase in rabbits conditioned to a schedule of alternating 12-hr periods of light and dark. Effects on blood-aqueous barrier permeability (K(d)), aqueous flow rate (F), outflow facility to general blood circulation (C(gen)), and uveoscleral outflow (F(u) were determined fluorophotometrically. Effects on ONH tissue circulation were estimated using the laser speckle method. Unilateral topical administration of 0.5% ifenprodil solution decreased intraocular pressure (IOP) with a maximum reduction of 3.4 mmHg and an effect duration of 3 hr without effects on the contralateral eye. A single instillation of 0.5% ifenprodil had no significant effect on K(d), F, or C(gen), whereas it substantially increased F(u). Twenty-day, twice-daily unilateral 0.5% ifenprodil instillation significantly increased tissue blood velocity in the ONH only in the treated eye.

Administration, Topical↗

PubMed2000

Effect of ifenprodil on ocular tissue circulation in rabbits.

Ifenprodil tartrate has long been employed as a cerebral vasodilator with alpha and N-methyl-D-aspartate (NMDA) receptor antagonistic activities. The purpose of this study was to evaluate the effects of ifenprodil on ocular circulation in rabbits. Experiments were performed during the dark phase in Dutch rabbits conditioned to a schedule of alternating 12-hr periods of light and dark. Effects on ocular tissue blood velocity were estimated using the laser speckle method in the iris, posterior choroid, and optic nerve head (ONH). Measurements of tissue blood velocity were performed both after intravenous injection of ifenprodil at a dose of 0.2 mg/kg, 0.1 mg/kg, and the same volume of the vehicle, and after topical instillation of 0.5% ifenprodil (50 microl) twice daily for 1, 3 and 20 days unilaterally in a masked manner. Intraocular pressure (IOP) was also measured during the experimental period. Intravenous administration of ifenprodil caused a significant increase in blood velocity in the ONH, choroid, and iris, but ONH circulation was affected at a lower dose than uveal circulation. In the topical instillation experiment, IOP in the ifenprodil-treated eye was significantly lower, by approximately 2 mmHg, than that in the contralateral eye when the laser speckle measurement was performed. Twice-daily, unilateral 0.5% ifenprodil instillation significantly increased blood velocity in the iris after 3 days and that in the ONH and posterior choroid after 20 days in the treated eye. Topical 0.5% ifenprodil increased blood velocity in the iris, posterior choroid, and ONH after multiple dosings. After systemic administration, ONH circulation appeared to be influenced at a lower dose than was uveal circulation.

Administration, Topical↗