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Purpose: The purpose of the current study was to assess the potential involvement of acid-sensing ion channel 1 (ASIC1) in retinal ganglion cell (RGC) death and investigate the neuroprotective effects of inhibitors of ASICs in promoting RGC survival following optic nerve crush (ONC). Results: ASIC1 protein was significantly increased in optic nerve extracts at day 7 following ONC in rats. Activated calpain-1 increased at 2 and 7 days following ONC as evidenced by increased degradation of α-fodrin, known substrate of calpain. Glial fibrillary acidic protein levels increased significantly at 2 and 7 days post-injury. By contrast, glutamine synthetase increased at 2 days while decreased at 7 days. The inhibition of ASICs with amiloride and psalmotoxin-1 significantly increased RGC survival in rats following ONC (p < 0.05, one-way ANOVA). The mean number of surviving RGCs in rats (n = 6) treated with amiloride (100 µM) following ONC was 1477 ± 98 cells/mm2compared with ONC (1126 ± 101 cells/mm2), where psalmotoxin-1 (1 μM) treated rats (n = 6) and subjected to ONC had 1441 ± 63 RGCs/mm2compared with ONC (1065 ± 76 RGCs/mm2). Average number of RGCs in control rats (n = 12) was 2092 ± 46 cells/mm2. Blocking of ASICs also significantly increased RGC survival from ischemic-like insult from 473 ± 80 to 842 ± 49 RGCs/mm2(for psalmotoxin-1) and from 628 ± 53 RGCs/mm2to 890 ± 55 RGCs/mm2(for amiloride) withp ≤ 0.05, using one-way ANOVA. Acidification (a known activator of ASIC1) increased intracellular Ca2+([Ca2+]i) in rat primary RGCs, which was statistically blocked by pretreatment with 100 nM psalmotoxin-1. Conclusions: ASIC1 up-regulation-induced influx of extracellular calcium may be responsible for activation of calcium-sensitive calpain-1 in the retina. Calpain-1 induced degradation of α-fodrin and leads to morphological changes and eventually neuronal death. Therefore, blockers of ASIC1 can be used as potential therapeutics in the treatment of optic nerve degeneration. Abbreviations:4-(2-Aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF); acid-sensing ion channels (ASICs); analysis of variance (ANOVA); bicinchoninic acid (BCA); brain-derived neurotrophic factor (BDNF); central nervous system (CNS); ciliary neurotrophic factor (CNTF); dimethyl sulfoxide (DMSO); endoplasmic reticulum (ER); ethylene glycol-bis(β-aminoethyl ether)-N,N,N’,N’-tetraacetic acid (EGTA); ethylenediaminetetraacetic acid (EDTA); Food and Drug Administration (FDA); glial fibrillary acidic protein (GFAP); glutamine synthetase (GS); intraocular pressure (IOP); kilodalton (kDa); Krebs-Ringer Buffer (KRB); optic nerve crush (ONC); phosphate-buffered saline (PBS); plasma membrane (PM); polymerase chain reaction (PCR); retinal ganglion cell (RGC); RNA Binding Protein With Multiple Splicing (RBPMS); room temperature (RT); standard error of the mean (SEM). [ABSTRACT FROM PUBLISHER]

The authors describe an immunocompetent, 50-year-old man who complained of a daily transient blurring of his vision with bilateral papilloedema. His visual acuity was 20/20 OU, and the blind spot was enlarged bilaterally. There was intracranial hypertension, but imaging for systemic and brain tumours were negative. These findings suggested a diagnosis of the pseudotumor syndrome. However, MRI showed leptomeningeal enhancement, and acetazolamide successfully resolved his visual symptoms and papilloedema. Cytology and flow cytometry of the CSF led to the final diagnosis of primary leptomeningeal lymphoma (PLML). Clinicians need to be aware that a case of PLML may be misdiagnosed as peudotumor cerebri. [ABSTRACT FROM AUTHOR]

An isolated unilateral abducens nerve palsy or headache alone usually yields negative findings on neuroimages. The authors report an individual with right abducens nerve palsy who developed a sudden, persistent headache on the right side. Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) revealed a giant aneurysm of the cavernous carotid artery that was located along the course of the right abducens nerve. The findings in this case of isolated abducens nerve palsy suggest that headaches should be considered as important signs for intracranial aneurysmal lesions. [ABSTRACT FROM AUTHOR]

We report two rare cases of biopsy proven Immunoglobulin G4-related sclerosing orbital inflammation (IgG4SOI). The first case had intracranial involvement which, to our knowledge, is the first IgG4SOI case with serum cerebrospinal fluid abnormalities and the second case had an unusual presentation of a compressive optic neuropathy and systemic lymphadenopathy. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the reasons why the intravitreal level of extracellular-superoxide dismutase (EC-SOD) increases in proliferative diabetic retinopathy patients by the investigation of two possibilities: first, change of EC-SOD expression in the retina; and secondly, leakage of EC-SOD through the endothelial monolayer by the treatment with endoplasmic reticulum (ER) stress inducers because ER stress is known to be involved in the vascular impairment in diabetic retinopathy. Intravitreous injection of tunicamycin in mice increased the permeability of tracer dye across retinal blood vessels while the retinal EC-SOD mRNA level was not changed. The leakage of EC-SOD through the retinal endothelial cell layer was elevated by the treatment with thapsigargin or tunicamycin. The expression of claudin-5 was significantly decreased by the treatment with the ER stress inducers. These phenomena were significantly suppressed by the pre-treatment of endothelial cells with a chemical chaperone 4-phenylbutyric acid. Our observations suggest that ER stress leads to the down-regulation of claudin-5 among tight junction proteins and may induce the elevation of endothelial permeability and leakage of EC-SOD into the vitreous body. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is regarded as a disease of the retinal microvascular system and metabolic abnormalities that are characteristic of oxidative stress and endoplasmic reticulum (ER) stress have been identified in the retina. Pericytes are known to be susceptible to oxidative stress and selective dropout of pericytes is one of the earliest pathological changes in DR. Extracellular-superoxide dismutase (EC-SOD) is a major antioxidative enzyme and protects vascular cells from the damaging effects of superoxide. Treatment with own conditioned medium significantly decreased EC-SOD expression in pericytes, while the expression of vascular endothelial growth factor and tumor necrosis factor-α were elevated. The addition of chemical chaperone 4-phenyl butyric acid significantly suppressed the effects of conditioned medium on EC-SOD and GRP78, a prominent ER-resident chaperone. Moreover, the cell viability of pericytes changed in a manner similar to that of EC-SOD expression. These results suggest that the expressions of EC-SOD should be regulated, at least partially, through ER stress. Continuous flow of culture media neutralized the ER-stress triggered decrease of EC-SOD expression. The stagnation of factors related to ER-stress around pericytes might reduce EC-SOD expression under pathophysiological conditions such as retinal edema, and this could induce and/or promote the intraretinal microvascular impairment and development of pathogenesis in DR. [ABSTRACT FROM AUTHOR]

A localized infarction at the junction of the optic nerve and chiasm (opto-chiasmal junction) is rare and difficult to detect by conventional neuro-imaging techniques. The purpose of this report is to show the diagnostic potential of diffusion-weighted magnetic resonance imaging for lesions at this location. A 62-year-old woman complained of sudden visual loss in her left eye. Visual field testing strongly suggested that the left opto-chiasmal junction was damaged. Diffusion weighted imaging demonstrated an area of restricted diffusion at the left opto-chiasmal junction, whereas the T2 weighted and fluid-attenuated inversion recovery sequences revealed no abnormality. [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]

Purpose: Repeated intravitreal injections of endothelin-1 (ET-1) lead to alterations in the visually evoked potentials (VEPs) and loss of retinal ganglion cells (RGCs) in rabbits. The purpose of this study was to determine whether kallidinogenase can offset the alterations induced by ET-1. Methods: ET-1 (2.5 × 10-7 M, 20 μ L) was injected into the vitreous of the right eye of rabbits (ET-1-treated eyes, n = 30) twice a week for 4 weeks. The vehicle for ET-1 was injected into the left eye on the same schedule (vehicle treated eyes, n = 30). During this 4 weeks period, kallidinogenase (1.0 unit/kg/day, kallidinogenase-treated group) or saline (saline-injected control group) was continuously delivered intravenously by an implanted osmotic pump. VEPs were recorded before, and 2 weeks and 4 weeks after, the first ET-1 injection, and all rabbits were sacrificed at 4 weeks. The number of RGC cells was counted in hematoxylin- and eosin-stained retinal sections. In the analyses, the ET-1 induced alterations were normalized to the values in the vehicle treated control eyes, i.e., kallidinogenase (K) + ET-1/K+ vehicle or saline (S) +ET-1/S + vehicle. Retinal sections were also examined by immunohistochemistry with antibodies to single-stranded DNA (ssDNA) or to glial fibrillary acidic protein (GFAP). The effect of kallidinogenase on the ONH blood flow was determined by a hydrogen gas clearance flowmeter. Results: The significant prolongation of the relative VEP implicit times (ITs) 4 weeks after the ET-1 injection (P < 0.01, paired t test; post-ET-1 vs. pre-ET-1) was significantly decreased by kallidinogenase (P < 0.001, t test, K + ET-1/K+ vehicle vs. S +ET-1/S + vehicle). The relative number of RGCs was decreased in the saline-injected group, and this decrease was also decreased by kallidinogenase (P < 0.05, t test, K + ET-1/K+ vehicle vs. S +ET-1/S + vehicle). ssDNA staining showed fewer apoptotic cells in the retina of kallidinogenase-treated rabbits. Intravitreal injection of ET-1 also decreased the blood flow in the optic nerve head and increased the GFAP immunostaining and axonal degeneration. These changes were also counteracted by kallidinogenase. Conclusion: These results indicate that kallidinogenase can counter the effects of ET-1 and should be considered for the treatment of ischemic retinal and optic nerve disorders related to abnormal ET-1 production. [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]

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]

The levels of IGF-I in the vitreous body and the intraocular fluid of patients with proliferative diabetic retinopathy (PDR) were determined using radioimmunoassay (RIA). Eleven vitreous specimens were obtained from the intraocular fluid of eyes of patients with PDR who underwent surgery during the operation. Eleven intraocular fluids from the same patients during reoperations were compared with controls. The expression of IGF-I mRNA in cultured human Muller glial cells was evaluated using reverse transcription-polymerase chain reaction (RT-PCR). The mean IGF-I level in the vitreous samples during initial PDR surgery and reoperation was significantly higher than that found in the vitreous of the control (p < 0.05). The level of IGF-I increased in 6 of the 11 cases. Cultured human Muller cells expressed IGF-I mRNA. The results indicate increased levels of IGF-I both in the initial vitreous and ocular fluid at post-operative reproliferation. Muller cell is suggested as an origin of local IGF-I production. [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]

To examine the reproducibility and sensitivity of flash visual evoked potential (VEP) testing in rabbits, we recorded the VEPs elicited by light stimuli in conscious rabbits from an active electrode placed on the primary visual cortex. We analyzed flash VEPs of rabbits by detecting the first negative peak, which was designated NI. We evaluated the effects of dark adaptation time (from 5 to 30min) on the latency and amplitude of NI, and the coefficient of variation (CV) of these parameters. Then, the intensity of photopic stimulation was varied using a neutral density (ND) filter from the standard o.6J to its -I.8 log unit energy level at 0.3 log unit decrements. The NI latency and amplitude were measured at each recording. There was no significant change in VEP latency or amplitude when the dark adaptation time was varied from 5 to 30 min (n = 7, P > 0.05, ANOVA). The CV of the NI latency was 0.4% and that of the NI amplitude was 4.2% (n = 6). The NI peak latency was prolonged and its amplitude decreased significantly with the decrease in the stimulus intensity; the changes in latency and amplitude relative to the standard were significant (n = I I, p < 0.001, ANOVA) and were strongly correlated with the reduction in the stimulus intensity (r = 0.90 and -0.80, respectively, Pearson's test). Also, the latencies and amplitudes were significantly different between all adjacent 0.3 and 0.6 log unit pairs of stimulus intensity, respectively. These results indicated that rabbit VEPs showed good reproducibility and a high sensitivity to light difference intensities, and that they may be useful not only to evaluate functional damage, but also to investigate the neuroprotective effect of drugs or cytokines. [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]

PURPOSE. To investigate whether or not human Müller cells synthesize interleukin (IL)-6. METHODS. Using RT-PCR, we first confirmed whether cultured human Müller cells express IL-6 mRNA. Then, to determine Müller cell IL-6 production after stimulation, cultured Müller cells were exposed to various concentrations of IL-1β (0.2 ng/ml, 2 ng/ml, 20 ng/ml) or lipopolysaccharide (LPS) (0.001 μg/ml, 0.1 μg/ml, 10 μg/ml) in 24 hr assays. In addition, to determine Müller cell time-dependent induction of IL-6 production, cultured Müller cells were exposed to IL-1β (0.02 ng/ml, 2 ng/ml) or LPS (10 μg/ml) for 6, 12, 24, 36 hr. IL-6 production in supernatants was quantified by ELISA. RESULTS. IL-6 mRNA was expressed in cultured human Müller cells, which produced IL-6 after stimulation with either IL-1β or LPS for 24 hours. IL-1β was a significantly more potent stimulator of IL-6 production than was LPS. Exposure of cultured human Müller cells to either IL-1β or LPS stimulated IL-6 production in a time-dependent fashion. CONCLUSIONS. Our findings indicate that human Müller cells can produce IL-6 when stimulated by IL-1β or LPS. Müller cell IL-6 production may have an important role in various conditions involving ocular inflammation. [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]

PURPOSE. The expression of Fas ligand (FasL) in ocular tissues is thought to play a critical role in maintaining immune privilege in the eye. In this study, to clarify the involvement of the Fas-FasL system in inflammatory processes of the eye,we examined soluble FasL (sFasL) in ocular inflammation. METHODS. Using ELISA systems recently developed, sFasL concentrations in aqueous humor (AH) and/or vitreous fluid (VF) were measured. AH was obtained from 17 eyes of 17 uveitis patients and from 12 eyes of 12 non-uveitis (cataract) patients. VF was obtained from 22 eyes of 22 uveitis patients and 7 eyes of 7 non-uveitis (macular hole) patients. Serum levels of sFasL were also determined. RESULTS. sFasL in AH and VF was below the detection limit of the ELISA systems in all non-uveitis eyes. On the other hand, sFasL was detected in AH from uveitis patients where it measured 367.0 ± 154.7 pg/ml (mean ± SEM). sFasL was also detected in VF from uveitis patients where it measured 1132.2 ± 281.7 pg/ml. None of the sera from patients with or without uveitis contained a detectable level of sFas L. CONCLUSIONS. sFasL levels in AH and VF are elevated in the eye during ocular inflammation. Fas-FasL mediated apoptosis may play an important role in the regulation of inflammation during uveitis. [ABSTRACT FROM AUTHOR]